The zinc-binding motif of human RECQ5beta suppresses the intrinsic strand-annealing activity of its DExH helicase domain and is essential for the helicase activity of the enzyme.
RecQ family helicases, functioning as caretakers of genomic integrity, contain a zinc-binding motif which is highly conserved among these helicases, but does not have a substantial structural similarity with any other known zinc-finger folds. In the present study, we show that a truncated variant of the human RECQ5beta helicase comprised of the conserved helicase domain only, a splice variant named RECQ5alpha, possesses neither ATPase nor DNA-unwinding activities, but surprisingly displays a strong strand-annealing activity. In contrast, fragments of RECQ5beta including the intact zinc-binding motif, which is located immediately downstream of the helicase domain, exhibit much reduced strand-annealing activity but are proficient in DNA unwinding. Quantitative measurements indicate that the regulatory role of the zinc-binding motif is achieved by enhancing the DNA-binding affinity of the enzyme. The novel intramolecular modulation of RECQ5beta catalytic activity mediated by the zinc-binding motif may represent a universal regulation mode for all RecQ family helicases.
Ren
Hua
H
CNRS, UMR 2027, Institut Curie-Section de Recherche, Centre Universitaire, Bâtiment 110, F-91405 Orsay, France.
Dou
Shuo-Xing
SX
Zhang
Xing-Dong
XD
Wang
Peng-Ye
PY
Kanagaraj
Radhakrishnan
R
Liu
Jie-Lin
JL
Janscak
Pavel
P
Hu
Jin-Shan
JS
Xi
Xu Guang
XG
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D004277:DNA, Single-Stranded / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D053484:RecQ Helicases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
D004277:DNA, Single-Stranded; C506732:RECQL5 protein, human; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D053484:RecQ Helicases