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Nucleic Acids Res October 15, 2015; 43 (18): 8790-800.

The N-terminus of RPA large subunit and its spatial position are important for the 5''->3'' resection of DNA double-strand breaks.

Tammaro M , Liao S , McCane J , Yan H .

The first step of homology-dependent repair of DNA double-strand breaks (DSBs) is the resection of the 5'' strand to generate 3'' ss-DNA. Of the two major nucleases responsible for resection, EXO1 has intrinsic 5''->3'' directionality, but DNA2 does not. DNA2 acts with RecQ helicases such as the Werner syndrome protein (WRN) and the heterotrimeric eukaryotic ss-DNA binding protein RPA. We have found that the N-terminus of the RPA large subunit (RPA1N) interacts with both WRN and DNA2 and is essential for stimulating WRN''s 3''->5'' helicase activity and DNA2''s 5''->3'' ss-DNA exonuclease activity. A mutant RPA complex that lacks RPA1N is unable to support resection in Xenopus egg extracts and human cells. Furthermore, relocating RPA1N to the middle subunit but not to the small subunit causes severe defects in stimulating DNA2 and WRN and in supporting resection. Together, these findings suggest that RPA1N and its spatial position are critical for restricting the directionality of the WRN-DNA2 resection pathway.

PubMed ID: 26227969
PMC ID: PMC4605295
Article link: Nucleic Acids Res
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cenpf ddc dna2 exo1 rpa1 wrn

Article Images: [+] show captions
References [+] :
Ball, ATRIP binding to replication protein A-single-stranded DNA promotes ATR-ATRIP localization but is dispensable for Chk1 phosphorylation. 2005, Pubmed