RECQ1 possesses DNA branch migration activity

被引:58
作者
Bugreev, Dmitry V. [1 ,2 ]
Brosh, Robert M., Jr. [3 ]
Mazin, Alexander V. [1 ]
机构
[1] Drexel Univ, Coll Med, Dept Biochem & Mol Biol, Philadelphia, PA 19102 USA
[2] Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Novosibirsk 630090, Russia
[3] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA
关键词
D O I
10.1074/jbc.M801582200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
RecQ helicases are essential for the maintenance of genome stability. Five members of the RecQ family have been found in humans, including RECQ1, RECQ5, BLM, WRN, and RECQ4; the last three are associated with human diseases. At this time, only BLM and WRN helicases have been extensively characterized, and the information on the other RecQ helicases has only started to emerge. Our current paper is focused on the biochemical properties of human RECQ1 helicase. Recent cellular studies have shown that RECQ1 may participate in DNA repair and homologous recombination, but the exact mechanisms of how RECQ1 performs its cellular functions remain largely unknown. Whereas RECQ1 possesses poor helicase activity, we found here that the enzyme efficiently promotes DNA branch migration. Further analysis revealed that RECQ1 catalyzes unidirectional three- stranded branch migration with a 3'-> 5' polarity. We show that this RECQ1 activity is instrumental in specific disruption of joint molecules (D- loops) formed by a 5' single- stranded DNA invading strand, which may represent dead end intermediates of homologous recombination in vivo. The newly found enzymatic properties of the RECQ1 helicase may have important implications for the function of RECQ1 in maintenance of genomic stability.
引用
收藏
页码:20231 / 20242
页数:12
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