E-Locus - Institutional Repository of the University of Crete - Η κινάση Chk1 προστατεύει από τις χρωματινικές γέφυρες φωσφορυλιώνοντας την πρωτεΐνη BLM στη Σερίνη 502 και εμποδίζοντας την αποικοδόμηση της

Home Η κινάση Chk1 προστατεύει από τις χρωματινικές γέφυρες φωσφορυλιώνοντας την πρωτεΐνη BLM στη Σερίνη 502 και εμποδίζοντας την αποικοδόμηση της

Results - Details

[Add to Basket]

Identifier

000388575

Title

Η κινάση Chk1 προστατεύει από τις χρωματινικές γέφυρες φωσφορυλιώνοντας την πρωτεΐνη BLM στη Σερίνη 502 και εμποδίζοντας την αποικοδόμηση της

Alternative Title

Chk1 protects against chromatin bridges by constitutively phosphorylating BLM Serine 502 to inhibit BLM degradation

Author

Δανδουλάκη, Μαρία Ε.

Thesis advisor

Ζάχος, Γεώργιος

Reviewer

Μαυροθαλασσίτης, Γεώργιος
Αθανασάκη, Ειρήνη
Πετσαλάκη, Ελένη

Abstract

DNA bridges represent incompletely segregated chromosomal DNA, connecting the poles of the two daughter cells during anaphase. If unresolved, DNA bridges can be fragmented during cytokinesis leading to chromosomal instability. Bloom’s syndrome protein, BLM, is localized in anaphase bridges and this localization is required for their resolution. Here, we show that Chk1 inhibition leads to BLM proteosomal degradation during interphase and higher frequency of chromatin bridges in anaphase. Chk1 constitutively phosphorylates BLM at Serine 502 (S502) in vivo and phosphorylated BLM localises to chromatin bridges. Mutation of Serine 502 of BLM to a phospho-mimicking BLM-S502D, in which S502 is mutated to aspartic acid, stabilises BLM and prevents chromatin bridges in Chk1 deficient cells. In addition, Cullin 3 ubiquitin ligase associates with wild-type but not BLM-S502D and Cullin 3 depletion stabilises BLM and rescues BLM localisation to chromatin bridges after Chk1 inhibition. These results suggest that Chk1 phosphorylates BLM at Serine 502 to inhibit Cullin 3-mediated BLM degradation by proteasome during interphase. We propose that Chk1 prevents DNA bridges in anaphase by stabilising BLM.

Language

Greek

Subject

Chromatin bridge

Cullin 3

Mitosis

Γέφυρες Χρωματίνης

Μίτωση

Issue date

2014-11-21

Collection

School/Department--School of Sciences and Engineering--Department of Biology--Post-graduate theses