3 DNA Replication End

8/18/2019 3 DNA Replication End

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Section 3

DNA Replication Process


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• Initiation: recognize the origine point,

separate dsDNA, primer synthesis, …

• Elongation: add dNTPs to the eisting

strand, !orm phosphodiester "onds,

correct the mismatch "ases, etending

the DNA strand, …

• Termination: stop the replication#

Replication is a continuous process , to describeit clearly, we separate it into three stage :


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Dna A

Dna BDna C

DNA topomerase

5'3'

3'

5'

primase

Primosome comple

B

a# Initiation


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目录

• dNTPs $hich is complementary to template are

contin%o%sly connected to the primer or the nascent

DNA chain "y DNA&pol III#

• The nat%re o! the chain elongation is the series

!ormation o! the phosphodiester "onds#

"# Elongation

http://../%E7%94%9F%E5%8C%966%E7%89%88/start.ppthttp://../%E7%94%9F%E5%8C%966%E7%89%88/start.ppthttp://../%E7%94%9F%E5%8C%966%E7%89%88/start.ppt


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Replication 'idelity

• Replication "ased on the principle o!"ase pairing is cr%cial to the highacc%racy o! the genetic in!ormation

trans!er#

• Enzymes %se t$o mechanisms toens%re the replication !idelity#

– Proo!reading and real&time correction

– (ase selection


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• The replication o! E. coli is

"idirectional !rom one origin, and the

t$o replication !or)s m%st meet at

one point called ter at 3*#

• All the primers $ill "e remo+ed, and

all the !ragments $ill "e connected "y DNA&pol I and ligase#

c# Termination


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3'

5'

5'

3'

RNAase

P-

3'

5'

5'

3'

DNA polymerase

P

3'

5'

5'

3'

dN!"

DNA ligase

3'

5'

5'

3'

A!"


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#3#* Replication o! E%)aryotes

• DNA replication is closely related $ith cellcycle#

• .%ltiple origins on one chromosome, and

replications are acti+ated sim%ltaneo%sly#


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•The terminal str%ct%re o! e%)aryoticDNA o! chromosomes is calledtelomere#

•

DNA se/%ence is rich in TTA000repeat se/%ence#

• The telomere str%ct%re is cr%cial to)eep the termini o! chromosomes#

Telomere


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• The e%)aryotic cells %se telomerase to

maintain the integrity o! DNA telomere#

•

Telomerase


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Re+erse transcription

Re+erse transcription is a process in

$hich ssRNA is %sed as the templateto synthesize dsDNA#


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Re+erse transcriptase

Re+erse transcriptase is the enzyme

!or the re+erse transcription# It has

acti+ity o! three )inds o! enzymes:

• RNA&dependent DNA polymerase

• RNase

• DNA&dependent DNA polymerase


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Section 1

DNA Damage and Repair


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.%tation is a change o! n%cleic acids in

genomic DNA o! an organism# Them%tation co%ld occ%r in the replication

process as $ell as in other steps o! li!e

process#

#1#2 .%tation


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1#* 4a%ses o! .%tation


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N

N ,

,

4-3

R

P

N

N ,

,

4-3

R

N

N ,

,

4-3

R

P

N

N ,R

$%

,

4-3

& ! !

'


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.%tation ca%sed "y chemicals

• 4arcinogens can ca%se m%tation#

• 4arcinogens incl%de:

• 'ood additi+es and !ood

preser+ati+es5 spoiled !ood

• Poll%tants: a%tomo"ile emission5

chemical $astes

• 4hemicals: pesticides5 al)yl

deri+ati+es5 &N-*- containing

materials


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Point m%tation is re!erred to as the

single n%cleotide alternation#

a# Point m%tation 6mismatch7

#1#3 Types o! .%tation

C ! ! C A ( ( A

( A A ( ! C C ( ( C (

5' 3'

3' 5'


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•

Transition: the "ase alternation !romp%rine to p%rine, or !rom pyrimidine

to pyrimidine#

• Trans+ersion: the "ase alternation

"et$een p%rine and pyrimidine, and

+ise +ersa#


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Transition m%tation


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-"A -"S

chains 4T4 4A4

mRNA 0A0 080

AA resid%e 9 in chain 0l% al

-" m%tation ca%sing Sic)le&cell o! anemia

Single

"ase m%tation leads to one AAchange, ca%sing disease#

Acidic AA 0l% change to Non&polar and hydropho"ic AA


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;hen P* decreased, -"S molec%lar

interaction, a helical polymer sol%"ility is lo$,

ca%ses R(4s to sic)le cell# The shape o! theR(4s $as +ery irreg%lar, large n%m"er o! thin,

elongated, sic)le&shaped !orms#

http://baike.baidu.com/image/027a45b5ddc03b8e36d3cacf


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"# Deletion and insertion

• Deletion: one or more n%cleotides are

deleted !rom the DNA se/%ence#

• Insertion: one or more n%cleotides

are inserted into the DNA se/%ence#

Deletion and insertion can ca%se the

reading !rame shi!ted#


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'rame&shi!t m%tation

Normal

1


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c# Rearrangement

It is the echang or trans!er o! genetic

in!ormation "et$een homologo%s

chromosome ,res%lting in the !ormationo! ne$ characteristics not !o%nd in

either parental DNA#


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0ene Rearrangement lead to mediterranean anemia

-" = gene !amily on

4hr 22


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• DNA repairing is a )ind response made"y cells a!ter DNA damage occ%rs,

$hich may res%me their nat%ral

str%ct%res and normal "iological!%nctions#

• DNA repairing is a s%pplementary to the

proo!reading&correction mechanism inDNA replication#

#1#> DNA Repairing


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N

N ,

,

4-3

R

P

N

N ,

,

4-3

R

N

N ,

,

4-3

R

P

N

N ,R

$%

,

4-3

& ! !

'

?ight repairing


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Ecision repairing

Recognise and clea+ein@%red !ragment "yendon%clease


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•

ne o! the most important ande!!ecti+e repairing approach#

• 8+rA and 8+r(: recognize and "ind

the damaged region o! DNA#

• 8+r4: ecise the damaged segment#

•

DNA&pol : synthesize the DNAsegment to !ill the gap#

• DNA ligase: seal the nic)#

Ecision repairing


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Recom"ination repairing

• It is %sed !or repairing $hen a large segmento! DNA is damaged#


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SS repairing

• It is responsi"le !or the sit%ation thatDNA is se+erely damaged and the

replication is hard to contin%e#

• I! $or)a"le, the cell co%ld "es%r+i+ed, "%t may lea+e many errors#

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