Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 284, Issue 14, Pages 9558-9565Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M808906200
Keywords
-
Categories
Funding
- Cancer Research UK
- European Community [LSHG-CT-2005512113]
- Genomic Instability in Cancer and Precancer [HEALTH-F22007-201630]
- Biotechnology and Biological Sciences Research Council Research [BBF0016651]
- BBSRC [BB/F001665/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F001665/1] Funding Source: researchfish
Ask authors/readers for more resources
In G(0) and G(1), DNA double strand breaks are repaired by non-homologous end joining, whereas in S and G(2), they are also repaired by homologous recombination. The human CtIP protein controls double strand break (DSB) resection, an event that occurs effectively only in S/G(2) and that promotes homologous recombination but not non-homologous end joining. Here, we mutate a highly conserved cyclin-dependent kinase (CDK) target motif in CtIP and reveal that mutating Thr-847 to Ala impairs resection, whereas mutating it to Glu to mimic constitutive phosphorylation does not. Moreover, we show that unlike cells expressing wild-type CtIP, cells expressing the Thr-to-Glu mutant resect DSBs even after CDK inhibition. Finally, we establish that Thr-847 mutations to either Ala or Glu affect DSB repair efficiency, cause hypersensitivity toward DSB-generating agents, and affect the frequency and nature of radiation-induced chromosomal rearrangements. These results suggest that CDK-mediated control of resection in human cells operates by mechanisms similar to those recently established in yeast.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available