Ren Hua, Dou Shuo-Xing, Zhang Xing-Dong, Wang Peng-Ye, Kanagaraj Radhakrishnan, Liu Jie-Lin, Janscak Pavel, Hu Jin-Shan, Xi Xu Guang
CNRS, UMR 2027, Institut Curie-Section de Recherche, Centre Universitaire, Bâtiment 110, F-91405 Orsay, France.
Biochem J. 2008 Jun 15;412(3):425-33. doi: 10.1042/BJ20071150.
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.
RecQ家族解旋酶作为基因组完整性的守护者，含有一个锌结合基序，该基序在这些解旋酶中高度保守，但与任何其他已知的锌指结构没有实质性的结构相似性。在本研究中，我们发现仅由保守解旋酶结构域组成的人RECQ5β解旋酶的截短变体，一种名为RECQ5α的剪接变体，既不具有ATP酶活性也不具有DNA解旋活性，但令人惊讶地表现出很强的链退火活性。相比之下，RECQ5β的片段包括完整的锌结合基序，该基序位于解旋酶结构域的紧下游，表现出大大降低的链退火活性，但擅长DNA解旋。定量测量表明，锌结合基序的调节作用是通过增强酶的DNA结合亲和力来实现的。由锌结合基序介导的RECQ5β催化活性的新型分子内调节可能代表了所有RecQ家族解旋酶的一种普遍调节模式。
