Correcons in our paperstoudai20168.up.seesaa.net/image/Y.Watanabe-Correction... · 2019-10-31 · AcPsm (2). tif FLAG AcPsm3 eso1+ (2) Psm (4).tif AcPsm(4).tif FLAG AcPsm3 eso1+ (4)

To whom it may concern,

After receiving anonymous allegations of research misconduct, the University of Tokyo conducted an investigation of seven articles published by my laboratory during 2005–2015. My colleagues and I have cooperated fully with the investigative committee, providing access to all raw data and participating in direct interviews. After an extensive investigation lasting eight months, the committee reported a number of errors in the handling of data in five of the seven papers in question. As the head of the laboratory, I take ultimate responsibility for these errors, and extend my sincerest apologies to the scientific community for any concern or inconvenience these may have caused. Although we believe that none of the errors affect the main conclusions of any of the reports, we are in contact with the journals in which they were published to determine the most appropriate action we should take for each of the articles (correction, retraction, etc.). In the interests of transparency and a speedy resolution to concerns about these articles, in the following slides I discloses the errors, steps now being taken to resolve them, and the implications for the conclusions of the respective publications. I provide both the originally published data and corrections (below). Again, I apologize deeply for any confusion that these errors may have caused.Sincerely,

Yoshinori Watanabe, PhD Laboratory of Chromosome Dynamics,Institute of Molecular and Cellular Biosciences, The University of Tokyo

コミュニティーの皆様へ　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　2017.6.17

このたび東京大学に対する匿名の論文不正の告発があり、私どもの研究室から出された７報の

論文について全てのデータに渡る詳細な調査を受けることになり、研究室を上げて全面的に調

査に協力してきました。８ヶ月に及ぶ調査の結果、５報の論文において、いくつかのデータの表示

において不適切な操作およびミスがあったことが調査委員会により指摘されました。私は今回の

調査結果を真摯に受け止め、これらの論文の責任著者として、論文に正確さに欠ける図表が

載ってしまったことに大きな責任を感じております。指摘を受けたいずれの記載も、当該論文自体

の科学的な結論に影響を与えるものではないと考えておりますが、論文の訂正あるいは取り下

げに関しましては、掲載誌と相談した上で最も適切な処置を速やかにとらせて頂く所存です。私

どもの論文疑惑が関連分野の研究者の皆様をいたずらに惑わすことのないように、委員会より

不適切の指摘を受けた記載についての詳細な情報と、それに対する生データに基づいた修正を、

以下に開示いたします。このたびの私どもの軽率な行いにより、研究者コミュニティーの皆様には

大変なご迷惑をおかけしましたことを心より陳謝いたします。

　　　　　　　　　　　　　　　　　東京大学分子細胞生物学研究所　染色体動態研究分野　渡邊嘉典

Anonymous allegations (and our responses): https://www.dropbox.com/s/3zwoop33r8x0c7k/Accusation%20%28E%29.pdf?raw=1

Two of the 23 allegations are raised in PubPeer: https://pubpeer.com/publications/20383139

https://pubpeer.com/publications/16325576

Correc&onsinourpapers

In Figs. 2e, 2f and 3d, the cells in the representative pictures expressed mCherry-Atb2 (tubulin), whereas the cells used in the quantification did not express mCherry-Atb2. During preparation of the manuscript, we mistakenly used a different population of cells during quantification, and due to this oversight we did not register the latter cells (i.e., those lacking mCherry-Atb2) in the published list of cell strains. However, because both of these cells are similarly arrested at metaphase I by inactivation of APC, the results of the quantification are closely similar and our conclusions are unaffected by this error. We have submitted a request to the journal for correction of the strain list. In Fig 4a, western blot panel of HP1α was improperly processed. We apologize for any confusion that these errors may have caused.

Yamagishi, Y., Sakuno, T., Shimura, M. & Watanabe, Y.Heterochromatin links to centromeric protection by recruiting shugoshin. Nature 455, 251-255 (2008)

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We confirmed that the quantitative intensities of Sgo1-GFP signal in mCherry-Atb2 expressing cells are nearly identical to those in cells lacking mCherry-Atb2. SD (n = 30 cells).

n.s. (t-test)

Correction

Uncropped image of blottings

PP2A-C

In Fig. 3A, two ChIP datasets (ChIP1 and ChIP2) were improperly combined into a single graph. In the corrected Fig. 3A, ChIP1 and ChIP2 are presented separately. These corrections do not affect the description of the results of the specific experiment or the conclusions of the article as a whole. We apologize for any confusion that this error may have caused.

Errors1)  Bir1(WT) and H3-pT3/H3(WT) derive only from ChIP1 but not ChIP2.2)  Experiment has not been performed, and should have been indicated as N.D. (not determined). 3)  There is a copy error in Swi6(swi6Δ).

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Published Fig. 3A

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Yamagishi, Y., Honda, T., Tanno, Y. & Watanabe, Y. Two histone marks establish the inner centromere and chromosome segregation. Science 330, 239-243 (2010)

Corrected Fig. 3A

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Tada, K., Susumu, H., Sakuno, T. & Watanabe, Y. Condensin association with histone H2A shapes mitotic chromosomes. Nature 474, 477-483 (2011)

In Figs. 3e, 3g, 5a and S16, the western blot panels were not properly processed. We show the corrected panels, which have been reconstructed from the raw data files, are shown here. These corrections do not affect the description of the results of the specific experiment or the conclusions of the article as a whole. We apologize for any confusion that this error may have caused.

EGFP-CAP-HSMC2

Tubulin

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Correction

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Correction

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Correction

CAP-H (Fig 3g)

Tubulin (Fig 3e) Cdc13 (Fig 5a)

SMC2

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H3

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Uncropped images of blottings

(Fig S16)

(fliphorizontal)

Fig 5a

Cnd2-pS5Cnd2-GFPCdc13H3-pS10

H3

0 15 30 45 60 75 (min)

Correction

Wehavereceivedanaffirma>vereplyfromNature.

CAP-HH2AH2B

H3

Input1% 0.1%

rIgG-IP

SMC2-IP

SMC2

H2A.ZActin

In Fig. 2A, western blot panels were misprocessed. Yoshinori Watanabe is responsible for this processing. The corrected figure is assembled from blots in the same experiment. This change does not affect the conclusion in the paper. We apologize for any confusion that this error may have caused.

Kagami, A., Sakuno, T., Yamagishi, Y., Ishiguro, T., Tsukahara, T., Shirahige, K., Tanaka, K., Watanabe, Y. Acetylation regulates monopolar attachment at multiple levels during meiosis I in fission yeast. EMBO Rep. 12, 1189-95 (2011)

AcPsm3FLAG

(Psm3)

eso1-H17eso1+

Experiment #4. Acetylation status of cohesin during meiosis

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anti-AcPsm3anti-FLAG

6/5

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2)

1)

3)

4)

Explanation for the left panels:The immunoprecipitation products prepared from eso1+ cells were analyzed by NuSDS PAGE, and blots were probed first with anti-AcPsm3 and then with anti-FLAG. This experiment was repeated four times, loading the same samples, until the IP samples were exhausted. None of the blots was perfect in terms of band loading and/or transfer, although 2), 3) and 4) are consistent. The red arrows show the published WBs; however, these were inappropriately taken from different WBs, which was not noted in the published figures. Moreover, background signals in the anti-Psm3 WB disappeared because the image contrast was increased in the published panel. Here, we provide a corrected version based on the original data, in which the WBs are indicated by blue arrows. We note that this version also supports the previous conclusion that ‘In meiosis, cohesin is acetylated depending on Eso1 also during late S phase and persists until prophase ‘.

Explanation for the left panels:IP products prepared from eso1-H17 cells were similarly analyzed and shown as a negative control (in both the previous and corrected versions).

This page is a copy of the progress report file by Dr. Kagami (June 10 2011).

Uncropped images of blottings(please note that all gels are flip horizontal)

Psm(2).tif

AcPsm(2).tifFLAG

AcPsm3

eso1+ (2)

Psm(4).tif

AcPsm(4).tif

FLAG

AcPsm3

eso1+ (4)

Psm(H17).tif

AcPsm(H17).tif

FLAG

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Published

Correction

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(Psm3)

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Addedon5thJune

Addedon7thJune

EMBO | Meyerhofstr.1 | 69117 Heidelberg | Germany phone +49 6221 8891 130 fax +49 6221 8891 200 www.embo.org

Dr. Bernd Pulverer Head of Scientific Publications

phone +49 6221 8891 501 fax +49 6221 8891 200

[email protected]

01.05.2017

Dr. Bernd Pulverer | EMBO | Meyerhofstr.1 | 69117 Heidelberg | Germany

YoshinoriWatanabe,PhD

LaboratoryofChromosomeDynamics,

InstituteofMolecularandCellularBiosciences,UniversityofTokyo,

Yayoi1-1-1,Tokyo113-0032,Japan

Re.:EMBOPressassessmentofpotentialimageaberrationinEMBORep.2011;12(11):1189-

95.doi:10.1038/embor.2011.188byYoshinoriWatanabeandcolleagues

DearYoshinori,

IhavewrittenaformallettertotheDr.Takeshitaoftheinvestigationcommitteethatoutlinesourassessmentoftheissuesin

the2011paper.Giventhelackofsignalinoneofthepanelsinparticular,wewouldsuggesttoissueashortcorrigendumthat

incudestheupdatedimagesfrommatchedWesternblotsbasedontheoriginalsourcedataoffigure2Aa.

Wewouldliketoinviteyoutoissuethistextandwewillaimtopublishitasfastaspossibleasacorrigenduminthejournal.

Tosummarizethiscase,youalertedustoapparentproblemsinfig2AonMarch29th2017,apparentlybasedonissues

pointedoutaspartoftheinstitutionalinvestigation.Weassessedallofthepublishedimagesofthepaperandfoundnoother

problemsthanthosenotedbyyouinfig2A.Regardingfig2A,weconcludethatthecontrastisoverlyaccentuatedinthe

Westernblotpanelsintheleftpartofthefigure,whichleadstoalossoflinearsignal,limitingthequantitativeinformation

thatcanbederivedfromtheimages.

YoualsorightlynotedthatthereisnoapparentsignalinthetoprighthandWesternblotpaneloffig2A.Thismaybedue

eithertothecompleteabsenceofexperimentaldataorimagesthatwereover-contrastedtothepointwhereallsignalislost

attheresolutionofthepublishedimage.Eitherway,panelswithnodetectabledataarenotinformative.Inthiscase,our

viewisthattheproblemismostlikelyeitherduetoamistakeortopoorimageprocessing,ratherthanintentional

falsification.

YoualsoprovidedasetofPowerPointfilesincludingsomeJapaneselanguageannotationsthatwecouldnotdecipher.These

filesappeartorepresentnotestakenatthetimebythepostdocwhoperformedtheexperimentsandyouconfirmedthat

thesefilesweresavedin2011.Youalsosuppliedasetofdigitalimagefilesthatapparentlyrepresentunprocessedsource

datascans.Wehaveassessedallofthesefilesandconcludethattheyareconsistentwithyourclaimthatyouranfoursetsof

Westernblotswiththesamesetofsamplesinparallelandprocessedtheseblotsinparallel(i.e.theyallderivedfromasingle

experiment).Theblotsunderlyingthedifferentpanelswereprobablyprocessedsomewhatdifferently,resultinginthe

differentcontrastandbackgroundnotedinthepublishedfigure.Thisclearlylimitsthequantitativecomparisonspossible

betweenthepanels,butnonethelessallowsforqualitativecomparisons.Theconclusionsinthepaperderivedfromthisfigure

arelargelyqualitativeandwethereforeseenocompellingreasontodoubttheseconclusions.Wedonothaveaccessto

primarylab-bookrecordsorindeedtheprimaryphotographsoftheWesternblots,theWesternblotsthemselvesor

remainingdenaturedproteinsamples,andassuchwecannotrunafullresearchinvestigationatEMBOPress.However,we

seenoreasontodoubtyourexplanations.

Werecommendissuingacorrigendumprimarilytopointtothefactthatthetoprightpanellackssignalandtoshowthe

correctpanels.Aspartofthiscorrigendum,wewouldalsoinviteyoutonotethattheWesternblotsinfig2Awerederived

fromthesamesamples,runatthesametime,butthatthesewereconcatenatedtoassemblethepublishedfigure.This

EMBO | Meyerhofstr.1 | 69117 Heidelberg | Germany phone +49 6221 8891 0 fax +49 6221 8891 202 [email protected] www.embo.org

resultedindifferentialcontrastandexposuresinthepublishedfigures,limitingthequantitativeinformationcontentofthe

figure,butnotpersetheconclusionsderived.

OntheEMBOPressscaleofimageaberrations(seeTheEMBOJournal(2015)34,2483-2485),thiswouldbealevel1,thelowestlevelon the scale we use to classify image and data aberrations (http://embor.embopress.org/classifying-image-aberrations).Thus,ourviewisthatthebasicconclusionsofthisfigure,andthereforethepaperasawhole,stand.Tobeclear,wedonotregarditasbestpracticetomixandmatchWesternblotpanelstoobtainthemost‘compelling’figure.

However,aslongasitistruethatthematchedblotsallderivedfromasinglesetofsamplesfromthesameexperiment,we

seenocaseofespeciallypoorexperimentalrigour,orindeedtoconcludeformalwrongdoing.

PleasenotethatwealsoassessedthefiguresofotherpapersthatyoukindlypublishedinjournalsthatbelongtotheEMBOPressgroup(listedbelow).Wedetectednootherissuesofimageaberrationormanipulationbasedonourstandardscreening

process.

Yourssincerely,

BerndPulverer,Ph.D.

HeadofScientificPublications;ChiefEditor,TheEMBOJournal;ActingChiefEditor,EMBOreports

OtherpapersassessedbyEMBOPressstandardimageforensicprocesses:

ThecohesinREC8preventsillegitimateinter-sistersynaptonemalcomplexassembly.IshiguroK,WatanabeY.EMBORep.2016Jun;17(6):783-4.doi:10.15252/embr.201642544.AcetylationregulatesmonopolarattachmentatmultiplelevelsduringmeiosisIinfissionyeast.KagamiA,SakunoT,YamagishiY,IshiguroT,TsukaharaT,ShirahigeK,TanakaK,WatanabeY.EMBORep.2011Oct28;12(11):1189-95.doi:10.1038/embor.2011.188.Anewmeiosis-specificcohesincompleximplicatedinthecohesincodeforhomologouspairing.IshiguroK,KimJ,Fujiyama-NakamuraS,KatoS,WatanabeY.EMBORep.2011Mar;12(3):267-75.doi:10.1038/embor.2011.2Auroracontrolssisterkinetochoremono-orientationandhomologbi-orientationinmeiosis-I.HaufS,BiswasA,LangeggerM,KawashimaSA,TsukaharaT,WatanabeY.EMBOJ.2007Oct31;26(21):4475-86.Rec8cleavagebyseparaseisrequiredformeioticnucleardivisionsinfissionyeast.KitajimaTS,MiyazakiY,YamamotoM,WatanabeY.EMBOJ.2003Oct15;22(20):5643-53.

In figs. 2C, S13C and S15A, the representative images for comparison were captured under different imaging conditions. In fig. S8B, S11F, S12B, the images used for compared were not adjusted using identical settings. In fig. S8A, the dot blots were mislabeled and not properly adjusted for contrast. We show corrected images or explanation here. Given that quantifications were performed using the original images, we believe that the changes in the representative images do not affect the conclusions of the paper. However, as this paper has a number of errors, we are contacting the journal to inquire whether extensive correction or retraction is more appropriate. We apologize for any confusion that these errors may have caused.

Tanno, Y., Susumu, H., Kawamura, M., Sugimura, H., Honda, T., & Watanabe, Y. The inner centromere-shugoshin network prevents chromosomal instability. Science 349, 1237-1240 (2015)

K9me3 blot

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fig S8A fig S8B Published

fig. S8In fig. S8A, western blots were mislabeled and not properly adjusted for contrast. In figure S8B, the pictures to be compared were not equally adjusted. Corrected panels are shown here. Panels for H3K9me3 staining were removed from fig S8B because they are shown in Figure 2C. Accordingly the figure legend is changed. These corrections do not affect either the description of the results in the paper or the conclusions contained therein.

K9me3 blot

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fig. S8�In fig. S8A, western blots were mislabeled and not properly adjusted for contrast (faint spot disappeared). In fig. S8B, the pictures to be compared were not equally adjusted. Correctly adjusted pictures are produced from the original files and shown here. These corrections do not affect either the description of the results in the paper or the conclusions contained therein.�

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Cold-treated and non-treated samples were prepared in parallel. The exposure conditions for filming tubulin signals are adjusted by the signal strength of each non-treated sample and applied to the cold-treated sample. Accordingly, the exposure time was different among samples. Quantification was done by the ratio between cold-treated and non-treated samples and normalized to that of control. The differences in exposure time compensate for differences in the intensity of staining between independent non-treated samples. Because imaging conditions were adjusted in a way that non-treated samples showed similar intensity, representative pictures of the cold-treated samples do reflect quantitative differences in the different conditions.

Explanation

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Fig. 1A�

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The graph in fig. S6 was assembled by extracting data from Fig. 1A. In this process, we have made a mistake in error bar addition. Corrected panel is shown here. �

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fig. S6�

0%

50%

100%100

50

0

Anap

hase

seg

rega

tion

erro

rs (%

)� StructureAttachment

HT10

80

HeLa

-3

293T

A172

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D

SW48

0Lo

voHT

29Ca

co2

Attachment defect

CIN+

Structure defect

0%

50%

100%100

50

0

Anap

hase

seg

rega

tion

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rs (%

)�

StructureAttachment

HT10

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HeLa

-3

293T

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A431

HeLa

-2

GM

637

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7

U2O

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SW48

0

Lovo

HT29

Caco

2

Attachment defect

CIN+

Structure defect

Fig. 1A�



The graph in fig. S6 was assembled by extracting data from Fig. 1A. In this process, we have made a mistake in error bar addition. Corrected panel is shown here. �


fig. S6�

0%

50%

100%100

50

0

Anap

hase

seg

rega

tion

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rs (%

)� StructureAttachment

HT10

80

HeLa

-3

293T

A172

A431

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-2

GM

637

MCF

7

U2O

ST4

7D

SW48

0Lo

voHT

29Ca

co2

Attachment defect

CIN+

Structure defect

Cells

with

coh

esio

n lo

ss a

fter

MG

132

arre

st (%

)

0

100

25

50

75

H4

HCT116

Cont

rol

siRAD

21

* * *

Co ntro l

s iS cc 1 H

4

0

2 5

5 0

7 5

1 0 0

Cells

with

coh

esio

n lo

ss a

fter

MG

132

arre

st (%

)

0

100

25

50

75

H4

HCT116

Cont

rol

siRAD

21

* * *

Published graph(± SEM)

Corrected graph(± SD)

fig. S13��fig. S6�

0%

50%

100%100

50

0

Anap

hase

seg

rega

tion

erro

rs (%

) StructureAttachment

HT10

80

HeLa

-3

293T

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-2

GM

637

MCF

7

U2O

ST4

7D

SW48

0Lo

voHT

29Ca

co2

Attachment defect

CIN+

Structure defect

Figure S6

01020304050

01020304050

0102030405060

293TU2OSA431

(iii) Doubly defective

Atta

chm

ent d

efec

t (%

)

(i) H3K9me3 defective

Atta

chm

ent d

efec

t (%

)

A

0102030405060

HCC1937(BRCA1)

MCF7HeLa-2 HeLa-3 GM637

- Su

v39

Soro

rin

HCT116(siRB)

(ii) Cohesindefective

Atta

chm

ent d

efec

t (%

)

0

10

20

30

40

50

******

**

***

**** ** **

Figure 4 A

- Su

v39

Soro

rin - Su

v39

Soro

rin - Su

v39

Soro

rin- Su

v39

Soro

rin

- Su

v39

Soro

rin -

Doub

le

Suv3

9 So

rorin

0

10

20

30

40

50

-

Doub

le

Suv3

9 So

rorin

-

Doub

le

Suv3

9 So

rorin




Fig. 1A�

Science 349, 1237-1240 (2015)

0%

50%

100%100

50

0

Anap

hase

seg

rega

tion

erro

rs (%


HT10

80

HeLa

-3

293T

A172

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D

SW48

0Lo

voHT

29Ca

co2

Attachment defect

CIN+

Structure defect

Figure S6

0102030405060


Atta

chm

ent d

efec

t (%

)

A

0102030405060

HCC1937(BRCA1)


- Su

v39

Soro

rin

**

**

***

Figure 4 A

- Su

v39

Soro

rin - Su

v39

Soro

rin - Su

v39

Soro

rin- Su

v39

Soro

rin

01020304050

01020304050

293TU2OSA431


Atta

chm

ent d

efec

t (%

)

HCT116(siRB)


Atta

chm

ent d

efec

t (%

)

0

10

20

30

40

50

**** ** **

- Su

v39

Soro

rin -

Doub

le

Suv3

9 So

rorin

0

10

20

30

40

50

-

Doub

le

Suv3

9 So

rorin

-

Doub

le

Suv3

9 So

rorin

****

*

Original graph and data(before revision)�Published graph Corrected graph

(all ± SEM)

In summary, both ICS network defects and mi-totic segregation errors are rescued by restor-ing H3K9me3 and/or cohesin in seven of nineCIN+ cells, which suggests that these two path-ways are important CIN-susceptible targets inhuman cells.Our study reveals that impairment in the ICS

network prevails among human CIN+ cell linesand acts as a key molecular mechanism to gen-erate CIN. Although numerous cellularmutationsmay influence chromosome segregation, onlymu-tations that moderately impair chromosome seg-regationwill establish CIN+ cells, which divide butexhibit genomic instability. In fact, the depletionof a core component of the ICS network (BUB1,SGO1, or the CPC) from cells provokes seriousmitotic defects that lead to lethalmitosis, whereashypomorphicmutations in the ICS network com-ponents cause CIN in cultured human cells andpromote tumorigenesis in mice (28, 29). None-

theless, mutations in components of the ICSnetwork (BUB1, SGO1, CPC) are rare in humancancer genomes (30), implying that the path-ways regulating the ICS network, rather than itscore components, might be genetically or epi-genetically alteredduring tumorigenesis. Indeed,we detected an ICS network defect associatedwith chromosome segregation errors in a patientwith non–small cell lung cancer (fig. S16). Futurestudies, including the inspection of a substantialnumber of clinical samples, will validate the po-tential linkage between ICS network defects andCIN in tumors.

REFERENCES AND NOTES

1. C. Lengauer, K. W. Kinzler, B. Vogelstein, Nature 396, 643–649(1998).

2. R. A. Burrell, N. McGranahan, J. Bartek, C. Swanton, Nature501, 338–345 (2013).

3. N. J. Ganem, S. A. Godinho, D. Pellman, Nature 460, 278–282(2009).

4. T. D. Barber et al., Proc. Natl. Acad. Sci. U.S.A. 105,3443–3448 (2008).

5. S. F. Bakhoum, G. Genovese, D. A. Compton, Curr. Biol. 19,1937–1942 (2009).

6. D. Cimini et al., J. Cell Biol. 153, 517–527 (2001).7. S. L. Thompson, D. A. Compton, J. Cell Biol. 180, 665–672

(2008).8. R. A. Burrell et al., Nature 494, 492–496 (2013).9. S. F. Bakhoum et al., Curr. Biol. 24, R148–R149 (2014).10. K. E. Gascoigne, S. S. Taylor, Cancer Cell 14, 111–122

(2008).11. D. A. Solomon et al., Science 333, 1039–1043 (2011).12. J. R. Daum et al., Curr. Biol. 21, 1018–1024 (2011).13. M. A. Lampson, I. M. Cheeseman, Trends Cell Biol. 21, 133–140

(2011).14. T. U. Tanaka, EMBO J. 29, 4070–4082 (2010).15. Y. Watanabe, Nat. Rev. Mol. Cell Biol. 13, 370–382 (2012).16. T. S. Kitajima et al., Nature 441, 46–52 (2006).17. Y. Tanno et al., Genes Dev. 24, 2169–2179 (2010).18. J. Lee et al., Nat. Cell Biol. 10, 42–52 (2008).19. K. J. Salimian et al., Curr. Biol. 21, 1158–1165 (2011).20. Y. Yamagishi, T. Sakuno, M. Shimura, Y. Watanabe, Nature

455, 251–255 (2008).21. T. Hirota, J. J. Lipp, B. H. Toh, J. M. Peters, Nature 438,

1176–1180 (2005).22. A. L. Nielsen et al., Mol. Cell 7, 729–739 (2001).23. P. A. Cloos et al., Nature 442, 307–311 (2006).24. H. Liu, L. Jia, H. Yu, Curr. Biol. 23, 1927–1933 (2013).25. J. M. Peters, A. Tedeschi, J. Schmitz, Genes Dev. 22,

3089–3114 (2008).26. M. L. Suvà, N. Riggi, B. E. Bernstein, Science 339, 1567–1570

(2013).27. T. Nishiyama et al., Cell 143, 737–749 (2010).28. K. Jeganathan, L. Malureanu, D. J. Baker, S. C. Abraham,

J. M. van Deursen, J. Cell Biol. 179, 255–267 (2007).29. H. Y. Yamada et al., Cell Cycle 11, 479–488 (2012).30. M. S. Lawrence et al., Nature 505, 495–501 (2014).

ACKNOWLEDGMENTS

We thank S. Hauf for critically reading the manuscript; T. Akiyama,Y. Gotoh, K. Shirahige, T. Hirota, K. Miyagawa, A. Enomoto,M. Ohsugi, T. Kitamura, H. Suzuki, and T. Ohta for kindly providingmaterials; K. Funai for clinical arrangements; Y. Hirabayashi,Y. Kanki, S. Koitabashi, M. Okada, T. Kahyo, A. R. Maia, R. Nakato,and D. Izawa for valuable technical advice; and all members of ourlaboratory, particularly Y. Yamagishi, for their valuable support anddiscussions. Supported by JSPS KAKENHI grants 24770180 and26440093 (Y.T.), a JSPS research fellowship (H. Sus.), and MEXTKAKENHI grants S-001 (H. Sug.) and 25000014 (Y.W.).

SUPPLEMENTARY MATERIALS

www.sciencemag.org/content/349/6253/1237/suppl/DC1Materials and MethodsFigs. S1 to S16References (31–40)

10 November 2014; accepted 5 August 201510.1126/science.aaa2655

1240 11 SEPTEMBER 2015 • VOL 349 ISSUE 6253 sciencemag.org SCIENCE

Fig. 4. Promotion of H3K9me3 andcohesin association with chromatinsuppress CIN. (A) The percentage ofanaphases showing attachment defectswas measured in the indicated cellsexpressing HA-Suv39H1-CENP-B and/orGFP-sororin. Error bars, SEM from threeindependent experiments. **P < 0.01,***P < 0.001, one-way ANOVA withBonferroni’s multiple comparisons test

relative to non-expressing cells. (B) Suppression of ICS network defects and CIN in various CIN+ cell lineswith defects (–) in H3K9me3 and chromatin-associated cohesin. The solid box indicates the suppression.

RESEARCH | REPORTSCorrected 18 September 2015; see full text.


(± SD)

(± SD)

Figure 4A

Figure 2A

11.21.41.61.82

2.2

RPE1

HCT1

16He

La-1

HT10

80

HeLa

-3

293T

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D

CIN- CIN+ (Attachment defect)

HP1α level in metaphase (centromere/arm)

* * * * *

* * * * * * * * * * * *

* * * * * * *

1.01.2

2.02.2

1.41.61.8

Corrected graph

11.21.41.61.82

2.2

RPE1

HCT1

16He

La-1

HT10

80

HeLa

-3

293T

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D



* * * * * * * * * * * * * * * *

* * * * * *

* *

1.01.2

2.02.2

1.41.62.2

Published graph


Cells

with

coh

esio

n lo

ss a

fter

MG

132

arre

st (%

)

0

100

25

50

75

H4

HCT116

Cont

rol

siRAD

21

* * *

Co ntro l

s iS cc 1 H

4

0

2 5

5 0

7 5

1 0 0

Cells

with

coh

esio

n lo

ss a

fter

MG

132

arre

st (%

)

0

100

25

50

75

H4

HCT116

Cont

rol

siRAD

21

* * *




0%

50%

100%100

50

0

Anap

hase

seg

rega

tion

erro

rs (%


HT10

80

HeLa

-3

293T

A172

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D

SW48

0Lo

voHT

29Ca

co2

Attachment defect

CIN+

Structure defect

Figure S6

01020304050

01020304050

0102030405060

293TU2OSA431


Atta

chm

ent d

efec

t (%

)


Atta

chm

ent d

efec

t (%

)

A

0102030405060

HCC1937(BRCA1)


- Su

v39

Soro

rin

HCT116(siRB)


Atta

chm

ent d

efec

t (%

)

0

10

20

30

40

50

******

**

***

**** ** **

Figure 4 A

- Su

v39

Soro

rin - Su

v39

Soro

rin - Su

v39

Soro

rin- Su

v39

Soro

rin

- Su

v39

Soro

rin -

Doub

le

Suv3

9 So

rorin

0

10

20

30

40

50

-

Doub

le

Suv3

9 So

rorin

-

Doub

le

Suv3

9 So

rorin




Fig. 1A�

Science 349, 1237-1240 (2015)

0%

50%

100%100

50

0

Anap

hase

seg

rega

tion

erro

rs (%


HT10

80

HeLa

-3

293T

A172

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D

SW48

0Lo

voHT

29Ca

co2

Attachment defect

CIN+

Structure defect

Figure S6

0102030405060


Atta

chm

ent d

efec

t (%

)

A

0102030405060

HCC1937(BRCA1)


- Su

v39

Soro

rin

**

**

***

Figure 4 A

- Su

v39

Soro

rin - Su

v39

Soro

rin - Su

v39

Soro

rin- Su

v39

Soro

rin

01020304050

01020304050

293TU2OSA431


Atta

chm

ent d

efec

t (%

)

HCT116(siRB)


Atta

chm

ent d

efec

t (%

)

0

10

20

30

40

50

**** ** **

- Su

v39

Soro

rin -

Doub

le

Suv3

9 So

rorin

0

10

20

30

40

50

-

Doub

le

Suv3

9 So

rorin

-

Doub

le

Suv3

9 So

rorin

****

*


(all ± SEM)



















ACKNOWLEDGMENTS










(± SD)

(± SD)

Figure 4A

Figure 2A

11.21.41.61.82

2.2

RPE1

HCT1

16He

La-1

HT10

80

HeLa

-3

293T

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D



* * * * *

* * * * * * * * * * * *

* * * * * * *

1.01.2

2.02.2

1.41.61.8

Corrected graph

11.21.41.61.82

2.2

RPE1

HCT1

16He

La-1

HT10

80

HeLa

-3

293T

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D



* * * * * * * * * * * * * * * *

* * * * * *

* *

1.01.2

2.02.2

1.41.62.2

Published graph




fig S13D

Science 349, 1237-1240 (2015)

0%

50%

100%100

50

0

Anap

hase

seg

rega

tion

erro

rs (%


HT10

80

HeLa

-3

293T

A172

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D

SW48

0Lo

voHT

29Ca

co2

Attachment defect

CIN+

Structure defect

Figure S6

0102030405060


Atta

chm

ent d

efec

t (%

)

A

0102030405060

HCC1937(BRCA1)


- Su

v39

Soro

rin

**

**

***

Figure 4 A

- Su

v39

Soro

rin - Su

v39

Soro

rin - Su

v39

Soro

rin- Su

v39

Soro

rin

01020304050

01020304050

293TU2OSA431


Atta

chm

ent d

efec

t (%

)

HCT116(siRB)


Atta

chm

ent d

efec

t (%

)

0

10

20

30

40

50

**** ** **

- Su

v39

Soro

rin -

Doub

le

Suv3

9 So

rorin

0

10

20

30

40

50-

Doub

le

Suv3

9 So

rorin

-

Doub

le

Suv3

9 So

rorin

****

*

Published graph Corrected graph(all ± SEM)



















ACKNOWLEDGMENTS










(± SD)

(± SD)

Fig 4A Fig 2A Published graph

Cells

with

coh

esio

n lo

ss a

fter

MG

132

arre

st (%

)

0

100

25

50

75

H4

HCT116

Cont

rol

siRAD

21

* * *

Co ntro l

s iS cc 1 H

4

0

2 5

5 0

7 5

1 0 0

Cells

with

coh

esio

n lo

ss a

fter

MG

132

arre

st (%

)

0

100

25

50

75

H4

HCT116

Cont

rol

siRAD

21

* * *




0%

50%

100%100

50

0

Anap

hase

seg

rega

tion

erro

rs (%


HT10

80

HeLa

-3

293T

A172

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D

SW48

0Lo

voHT

29Ca

co2

Attachment defect

CIN+

Structure defect

Figure S6

01020304050

01020304050

0102030405060

293TU2OSA431


Atta

chm

ent d

efec

t (%

)


Atta

chm

ent d

efec

t (%

)

A

0102030405060

HCC1937(BRCA1)


- Su

v39

Soro

rin

HCT116(siRB)


Atta

chm

ent d

efec

t (%

)

0

10

20

30

40

50

******

**

***

**** ** **

Figure 4 A

- Su

v39

Soro

rin - Su

v39

Soro

rin - Su

v39

Soro

rin- Su

v39

Soro

rin

- Su

v39

Soro

rin -

Doub

le

Suv3

9 So

rorin

0

10

20

30

40

50

-

Doub

le

Suv3

9 So

rorin

-

Doub

le

Suv3

9 So

rorin




Fig. 1A�

Science 349, 1237-1240 (2015)

0%

50%

100%100

50

0

Anap

hase

seg

rega

tion

erro

rs (%


HT10

80

HeLa

-3

293T

A172

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D

SW48

0Lo

voHT

29Ca

co2

Attachment defect

CIN+

Structure defect

Figure S6

0102030405060


Atta

chm

ent d

efec

t (%

)

A

0102030405060

HCC1937(BRCA1)


- Su

v39

Soro

rin

**

**

***

Figure 4 A

- Su

v39

Soro

rin - Su

v39

Soro

rin - Su

v39

Soro

rin- Su

v39

Soro

rin

01020304050

01020304050

293TU2OSA431


Atta

chm

ent d

efec

t (%

)

HCT116(siRB)


Atta

chm

ent d

efec

t (%

)

0

10

20

30

40

50

**** ** **

- Su

v39

Soro

rin -

Doub

le

Suv3

9 So

rorin

0

10

20

30

40

50

-

Doub

le

Suv3

9 So

rorin

-

Doub

le

Suv3

9 So

rorin

****

*


(all ± SEM)



















ACKNOWLEDGMENTS










(± SD)

(± SD)

Figure 4A

Figure 2A

11.21.41.61.82

2.2

RPE1

HCT1

16He

La-1

HT10

80

HeLa

-3

293T

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D



* * * * *

* * * * * * * * * * * *

* * * * * * *

1.01.2

2.02.2

1.41.61.8

Corrected graph

11.21.41.61.82

2.2

RPE1

HCT1

16He

La-1

HT10

80

HeLa

-3

293T

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D



* * * * * * * * * * * * * * * *

* * * * * *

* *

1.01.2

2.02.2

1.41.62.2

Published graph


Cells

with

coh

esio

n lo

ss a

fter

MG

132

arre

st (%

)

0

100

25

50

75

H4

HCT116

Cont

rol

siRAD

21

* * *

Co ntro l

s iS cc 1 H

4

0

2 5

5 0

7 5

1 0 0

Cells

with

coh

esio

n lo

ss a

fter

MG

132

arre

st (%

)

0

100

25

50

75

H4

HCT116

Cont

rol

siRAD

21

* * *




0%

50%

100%100

50

0

Anap

hase

seg

rega

tion

erro

rs (%


HT10

80

HeLa

-3

293T

A172

A431

HeLa

-2

GM

637

MCF

7

U2O

ST4

7D

SW48

0Lo

voHT

29Ca

co2

Attachment defect

CIN+

Structure defect

Figure S6

01020304050

01020304050

0102030405060

293TU2OSA431


Atta

chm

ent d

efec

t (%

)


Atta

chm

ent d

efec

t (%

)

A

0102030405060

HCC1937(BRCA1)


- Su

v39

Soro

rin

HCT116(siRB)


Atta

chm

ent d

efec

t (%

)

0

10

20

30

40

50

******

**

***

**** ** **

Figure 4 A

- Su

v39

Soro

rin - Su

v39

Soro

rin - Su

v39

Soro

rin- Su

v39

Soro

rin

- Su

v39

Soro

rin -

Doub

le

Suv3

9 So

rorin

0

10

20

30

40

50

-

Doub

le

Suv3

9 So

rorin

-

Doub

le

Suv3

9 So

rorin




Fig. 1A�

Science 349, 1237-1240 (2015)

0%

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Figure S6

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Figure 4 A

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*


(all ± SEM)



















ACKNOWLEDGMENTS










(± SD)

(± SD)

Figure 4A

Figure 2A

11.21.41.61.82

2.2

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HCT1

16He

La-1

HT10

80

HeLa

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293T

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GM

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7

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* * * * *

* * * * * * * * * * * *

* * * * * * *

1.01.2

2.02.2

1.41.61.8

Corrected graph

11.21.41.61.82

2.2

RPE1

HCT1

16He

La-1

HT10

80

HeLa

-3

293T

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HeLa

-2

GM

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7

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7D



* * * * * * * * * * * * * * * *

* * * * * *

* *

1.01.2

2.02.2

1.41.62.2

Published graph



Corrected graph

We additionally made some inadvertent mistakes (due to a mistake in our use of the graph software) in adding error bars in Fig. 2A, 4A, S6 and S13D, while preparing or revising the manuscript. We have confirmed that the statistical analyses are all valid, as they were performed on the original data. The errors are corrected here. We apologize for any confusion that these errors may have caused.

fig S12B Published Correction or retraction of the figure

fig S6


Published graph Corrected graph

FigS12B�

Correctlyadjusted(retryat21May)�

Published�

Control� siRB� siBRCA1�

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G1 G2 G1 G2 G1 G2

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HCT116 B

FigS12B�

Correctlyadjusted(retryat21May)�

Published�


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G1 G2 G1 G2 G1 G2

HCT116 B


RAD

21

DN

A�Au

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B�

G1 G2 G1 G2 G1 G2

HCT116 B

Documents

Correcons in our paperstoudai20168.up.seesaa.net/image/Y.Watanabe-Correction... · 2019-10-31 · AcPsm (2). tif FLAG AcPsm3 eso1+ (2) Psm (4).tif AcPsm(4).tif FLAG AcPsm3 eso1+ (4)