human exonuclease 1 and BLM helicase

In a recent paper by Amitabh Nimonkar and colleagues, it was established that human BLM helicase, a member of the RecQ family, stimulates human exonuclease 1 (hExo1), a 5′ – 3′ double-stranded DNA exonuclease … “Stimulation of DNA resection by hExo1 is independent of BLM helicase activity and is, instead, mediated by an interaction between the 2 proteins. DNA ends resected by hExo1 and BLM are used by human Rad51, but not its yeast or bacterial counterparts, to promote homologous DNA pairing.”

Nimonkar AV, Oözsoy AZ, Genschel J, Modrich P, Kowalczykowski SC.
Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair.
Proc Natl Acad Sci U S A. 2008 Oct 29. [Epub ahead of print]

WRN mini-review

In a recent issue of DNA Repair [7 (2008) 1776–1786], Julia Sidorova reviews the role of WRN in preserving DNA integrity during replication and propose that WRN can function in coordinating replication fork progression with replication stress-induced fork remodeling. She further discusses damage tolerance pathways, redundancy, and cooperation with other RecQ helicases.

Fig. 3. Possible scenarios of WRN function in coordinating fork progression with damage repair via control over daughter/daughter duplex expansion and/or half-life. (A) An unproductive daughter/daughter duplex with the 3′ overhang is unwound to redirect damage bypass towards translesion synthesis (TLS). (B) An extension of a daughter/daughter duplex leads to exposure of ssDNA regions of mother strands (for simplicity, only one of the strands is shown coated with RPA). Accumulation of RPA stimulates helicase activity of WRN to limit propagation of daughter/daughter duplex and restore an original fork conformation. (C) Lagging strand synthesis in the presence of a daughter/daughter duplex can lead to formation of long flaps. WRN can prevent their formation by limiting half-life of a daughter/daughter duplex, or stimulate FEN-1 to cleave such flaps once they are formed.