RECQL5 plays co-operative and complementary roles with WRN syndrome helicase.

[werner syndrome]

Humans have five RecQ helicases , whereas simpler organisms have only one . Little is known about whether and how these RecQ helicases co -operate and /or complement each other in response to cellular stress . Here we show that RECQL 5 associates longer at laser-induced DNA double -strand breaks in the absence of Werner syndrome (WRN ) protein , and that it interacts physically and functionally with WRN both in vivo and in vitro . RECQL 5 co -operates with WRN on synthetic stalled replication fork-like structures and stimulates its helicase activity on DNA fork duplexes . Both RECQL 5 and WRN re -localize from the nucleolus into the nucleus after replicative stress and significantly associate with each other during S-phase . Further , we show that RECQL 5 is essential for cell survival in the absence of WRN . Loss of both RECQL 5 and WRN severely compromises DNA replication , accumulates genomic instability and ultimately leads to cell death . Collectively , our results indicate that RECQL 5 plays both co -operative and complementary roles with WRN . This is an early demonstration of a significant functional interplay and a novel synthetic lethal interaction among the human RecQ helicases .