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LE “CODE” ISTONICHE E LA REGOLAZIONE
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005Nature 2010
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
Cromodominio
Dominio cromo ombra
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
Riconoscimento acetilisina bromodominio
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
`BRD fold'.
56 BRD in human genomeTAFs
Berg et al., BIOCHIMICA 6/E, Zanichelli editore S.p.A. Copyright © 2007
CEN
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
/H3
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
/H3
Science 2010
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
For proper partitioning of chromosomes in mitosis, the chromosomal passenger complex (CPC- including Aurora B and survivin) must be localized at the center of paired kinetochores, at the site called the inner centromere. How the CPC is targeted to this site?.
The phosphorylation of histone H3–threonine 3 (H3-pT3) mediated by Haspincooperates with Bub1-mediated histone 2A–serine 121 (H2A-S121) phosphorylation in targeting the CPC to the inner centromere
H3-pT3 promotes nucleosome binding of survivin, whereas phosphorylated H2A-
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
H3-pT3 promotes nucleosome binding of survivin, whereas phosphorylated H2A-S121 facilitates the binding of shugoshin, the centromeric CPC adaptor.
Haspin colocalizes with cohesin by associating with Pds5, whereas Bub1 localizes at kinetochores.
Thus, the inner centromere is defined by intersection of two histone kinases.
The chromosomal passenger complex CPC
influences spindle checkpoint activity indirectly, through the creation of unattached kinetochores. Upon entry into mitosis chromosomes start to make random connections with microtubules from the mitotic spindle. To finally obtain bipolar spindle attachments, improper attachments (syntelic attachments) need to be corrected to prevent chromosome segregation errors. Aurora B in complex with its fellow passenger proteins is necessary for this correction process.
Through the phosphorylation of kinetochore proteins that bind microtubules it modifies the stability or affinity of the kinetochore-microtubule interaction. of the kinetochore-microtubule interaction.
As a consequence microtubules detach from the kinetochore allowing new rounds of attachments until bipolarity is obtained.
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
Chinasi
chromosomal passenger complex
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
Cell extracts prepared were immunoblotted for H3-pT3 and H3.
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
Hrk1 (Haspin) is the sole kinase phosphorylating H3-T3 in vivoPhosphorylation is abolished in h3-TA cells in which Thr3 is replaced with alanine (H3-TA)
G2; asynchronous culture, M; prometaphase arrest
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
5-flourouracil (5-FU)-sincronizzazione in prometafase
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
Watson et al., BIOLOGIA MOLECOLARE DEL GENE, Zanichelli editore S.p.A. Copyright © 2005
