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酿酒酵母Mer3解旋酶刺激Rad51介导的3'-5'异源双链延伸;对减数分裂重组中交叉控制的影响。

Saccharomyces cerevisiae Mer3 helicase stimulates 3'-5' heteroduplex extension by Rad51; implications for crossover control in meiotic recombination.

作者信息

Mazina Olga M, Mazin Alexander V, Nakagawa Takuro, Kolodner Richard D, Kowalczykowski Stephen C

机构信息

Ludwig Institute for Cancer Research, Cancer Center and Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USA.

出版信息

Cell. 2004 Apr 2;117(1):47-56. doi: 10.1016/s0092-8674(04)00294-6.

Abstract

Crossover and noncrossover recombinants can form by two different pathways during meiotic recombination in Saccharomyces cerevisiae. The MER3 gene is known to affect selectively crossover, but not noncrossover, recombination. The Mer3 protein is a DNA helicase that unwinds duplex DNA in the 3' to 5' direction. To define the underlying molecular steps of meiotic recombination, we investigated the role of Mer3 helicase in DNA strand exchange promoted by Rad51 protein. We found that Mer3 helicase does not function as an initiator of DNA pairing events but, rather, it stimulates DNA heteroduplex extension in the 3' --> 5' direction relative to the incoming (or displaced) single-stranded DNA. Conversely, Mer3 helicase blocks DNA heteroduplex extension in the 5' --> 3' direction. Our results support the idea that Mer3 helicase stabilizes nascent joint molecules via DNA heteroduplex extension to permit capture of the second processed end of a double-stranded DNA break, a step which is required for crossover recombinant product formation.

摘要

在酿酒酵母减数分裂重组过程中,交叉和非交叉重组体可通过两种不同途径形成。已知MER3基因选择性地影响交叉重组,而非非交叉重组。Mer3蛋白是一种DNA解旋酶,可沿3'至5'方向解开双链DNA。为了确定减数分裂重组的潜在分子步骤,我们研究了Mer3解旋酶在由Rad51蛋白促进的DNA链交换中的作用。我们发现,Mer3解旋酶并非作为DNA配对事件的起始者发挥作用,相反,相对于进入(或被置换)的单链DNA,它刺激DNA异源双链在3'→5'方向上延伸。相反,Mer3解旋酶会阻止DNA异源双链在5'→3'方向上延伸。我们的结果支持这样一种观点,即Mer3解旋酶通过DNA异源双链延伸来稳定新生的连接分子,从而允许捕获双链DNA断裂的第二个加工末端,这是交叉重组产物形成所必需的一步。

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