Journal
CELL RESEARCH
Volume 24, Issue 5, Pages 532-541Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cr.2014.36
Keywords
Rad51; Ago2; diRNA; Homologous recombination; DSB
Categories
Funding
- National Basic Research Program of China (973 Program) [2011CB510103, 2012CB910900]
- National Natural Science Foundation of China [31225015, 31370796, 31150110143]
- CAS Young Foreign Fellow Award [2010Y2SB14]
- Danish Council for Independent Research - Medical Sciences (JMRD)
- CAS 100-talents Professor Program
Ask authors/readers for more resources
DNA double-strand breaks (DSBs) are highly cytotoxic lesions and pose a major threat to genome stability if not properly repaired. We and others have previously shown that a class of DSB-induced small RNAs (diRNAs) is produced from sequences around DSB sites. DiRNAs are associated with Argonaute (Ago) proteins and play an important role in DSB repair, though the mechanism through which they act remains unclear. Here, we report that the role of diRNAs in DSB repair is restricted to repair by homologous recombination (HR) and that it specifically relies on the effector protein Ago2 in mammalian cells. Interestingly, we show that Ago2 forms a complex with Rad51 and that the interaction is enhanced in cells treated with ionizing radiation. We demonstrate that Rad51 accumulation at DSB sites and HR repair depend on catalytic activity and small RNA-binding capability of Ago2. In contrast, DSB resection as well as RPA and Mre11 loading is unaffected by Ago2 or Dicer depletion, suggesting that Ago2 very likely functions directly in mediating Rad51 accumulation at DSBs. Taken together, our findings suggest that guided by diRNAs, Ago2 can promote Rad51 recruitment and/or retention at DSBs to facilitate repair by HR.
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