title: RECQL5 plays co-operative and complementary roles with WRN syndrome helicase.
abstract: 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 RECQL5 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. RECQL5 co-operates with WRN on synthetic stalled replication fork-like structures and stimulates its helicase activity on DNA fork duplexes. Both RECQL5 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 RECQL5 is essential for cell survival in the absence of WRN. Loss of both RECQL5 and WRN severely compromises DNA replication, accumulates genomic instability and ultimately leads to cell death. Collectively, our results indicate that RECQL5 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.
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
authors.forename: Venkateswarlu
authors.initials: V
authors.lastname: Popuri
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Mahesh
authors.initials: M
authors.lastname: Ramamoorthy
authors.forename: Takashi
authors.initials: T
authors.lastname: Tadokoro
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Croteau
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
mesh_terms: D002460:Cell Line; D002470:Cell Survival; D053903:DNA Breaks, Double-Stranded; D004261:DNA Replication; D005090:Exodeoxyribonucleases / Q000378:metabolism* / Q000502:physiology; D042822:Genomic Instability; D053484:RecQ Helicases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D014898:Werner Syndrome / Q000235:genetics; D000071657:Werner Syndrome Helicase
chemical_list: C506732:RECQL5 protein, human; D005090:Exodeoxyribonucleases; C097151:Bloom syndrome protein; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase