A positive involvement of RecQL4 in UV-induced S-phase arrest.
RecQL4 belongs to a family of conserved RECQ helicases that are important in maintaining chromosomal integrity. Human patients lacking RecQL4 showed extreme sensitivity to UV and oxidation damage, suggesting that RecQL4 is involved in the damage signaling and/or repair. Here we show that human mutant cells lacking RecQL4 were defective in UV-induced S-phase arrest, whereas cells defective in bloom syndrome protein (BLM), another member of RecQ family exhibited a normal S-phase arrest following UV irradiation. In keeping with this, a targeted inhibition of RecQL4 expression in human 293 cells showed a defect in inducing S-phase (replication) arrest following UV treatment. Human mutant cells lacking RecQL4 protein were also defective in inducing S-phase arrest following hydroxyurea treatment. Together, our results suggest that RecQL4 may have a unique role in replication fork arrest, which may not be shared with other members of RecQ family such as BLM.
Park
Su-Jung
SJ
Department of Biochemistry and Molecular Biology, Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Lee
Young-Ju
YJ
Beck
Brian D
BD
Lee
Suk-Hee
SH
D000251:Adenosine Triphosphatases / Q000235:genetics; D002478:Cells, Cultured; D004265:DNA Helicases / Q000235:genetics; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D053484:RecQ Helicases / Q000235:genetics / Q000502:physiology*; D016196:S Phase / Q000528:radiation effects*; D014466:Ultraviolet Rays
D004273:DNA, Neoplasm; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; C506731:RECQL4 protein, human; D004265:DNA Helicases; D053484:RecQ Helicases; D006918:Hydroxyurea