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RECQL5 plays both co‐operative and complementary roles with WRN syndrome helicase.
Author(s) -
Popuri Venkateswarlu,
Huang Jing,
Mahesh Ramamoorthy,
Tadokoro Takashi,
Deborah Croteau L,
Bohr Vilhelm A.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.542.1
Subject(s) - helicase , biology , genome instability , werner syndrome , recq helicase , nucleolus , dna repair , microbiology and biotechnology , dna replication , genetics , dna damage , bloom syndrome , dna , gene , nucleus , rna
Humans have five RecQ helicases whereas lower organisms like bacteria and yeast have only one member per species. Little is known about whether and how these RecQ helicases cooperate and/or complement each other in response to cellular stress. Here we show that RECQL5 associates longer at laser‐induced DNA double strand breaks (DSBs) 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.