In:
Journal of Cell Biology, Rockefeller University Press, Vol. 194, No. 5 ( 2011-09-05), p. 705-720
Abstract:
DNA double-strand break (DSB) resection, which results in RPA-bound single-stranded DNA (ssDNA), is activated in S phase by Cdk2. RPA-ssDNA activates the ATR-dependent checkpoint and homology-directed repair (HDR) via Rad51-dependent mechanisms. On the other hand, the fate of DSBs sustained during vertebrate M phase is largely unknown. We use cell-free Xenopus laevis egg extracts to examine the recruitment of proteins to chromatin after DSB formation. We find that S-phase extract recapitulates a two-step resection mechanism. M-phase chromosomes are also resected in cell-free extracts and cultured human cells. In contrast to the events in S phase, M-phase resection is solely dependent on MRN-CtIP. Despite generation of RPA-ssDNA, M-phase resection does not lead to ATR activation or Rad51 chromatin association. Remarkably, we find that Cdk1 permits resection by phosphorylation of CtIP but also prevents Rad51 binding to the resected ends. We have thus identified Cdk1 as a critical regulator of DSB repair in M phase. Cdk1 induces persistent ssDNA-RPA overhangs in M phase, thereby preventing both classical NHEJ and Rad51-dependent HDR.
Type of Medium:
Online Resource
ISSN:
1540-8140
,
0021-9525
DOI:
10.1083/jcb.201103103
Language:
English
Publisher:
Rockefeller University Press
Publication Date:
2011
detail.hit.zdb_id:
1421310-2
SSG:
12
