雙鏈斷裂的DNA能夠以其同源染色體為模板,通過同源重組的方式修復(fù),,這一過程對DNA復(fù)制,、DNA損傷的修復(fù)及減數(shù)分裂中重組和同源染色體分離等有重要作用。
在減數(shù)分裂過程中,,由Spo11蛋白質(zhì)催化形成斷裂雙鏈,,RecA族蛋白結(jié)合于斷裂的DNA末端形成DNA-蛋白 質(zhì)細絲,能夠催化同源配對,,使單鏈DNA末端入侵其同源區(qū)段,,Rad51和Dmc1兩個RecA的同源蛋白在此過程中起重要作用。但是科學(xué)家對入侵后的同源重組過程則了解得比較少,。
來自美國加利福尼亞大學(xué)和日本大阪大學(xué)的研究人員以芽殖酵母為研究對象,,采用雙向電泳和Southern雜交等主要技術(shù),對同源重組的入侵后過程進行研究,,結(jié)果發(fā)現(xiàn)無論交換和非交換的同源重組,,Rad52在入侵后過程中均起重要作用,能夠催化DNA互補序列退火,,該活性存在于Rad52的N末端結(jié)構(gòu)域,。
在前期DNA末端入侵同源染色體時,Rad51的結(jié)合也必需由Rad52催化,,而在入侵后階段Rad52自身能夠催化DNA互補序列退火,,并且和Rad51的富集無關(guān)??梢奟ad52在通過同源重組修復(fù)斷裂雙鏈的不同階段均有著非常重要的作用,,與同源互補序列的退火密切相關(guān)。異常交換可能導(dǎo)致染色體重排,、同源染色體的錯誤分離等致命突變,,而適當(dāng)調(diào)節(jié)Rad52的活性可能抑制異常交換的發(fā)生。
該研究結(jié)果發(fā)表于2008年2月29日的《分子細胞》(Molecular Cell)雜志上,。(科學(xué)網(wǎng) 穆宏平/編譯)
生物谷推薦原始出處:
(Molecular Cell),,Vol 29, 517-524, 29 February 2008,Jessica P. Lao, Neil Hunter
Rad52 Promotes Postinvasion Steps of Meiotic Double-Strand-Break Repair
Jessica P. Lao,1,2 Steve D. Oh,1,2 Miki Shinohara,3 Akira Shinohara,3 and Neil Hunter1,2,
1 Section of Microbiology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
2 Section of Molecular and Cellular Biology, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA
3 Institute for Protein Research, Graduate School of Science, Osaka University, Suita 565-0871, Japan
Corresponding author
Neil Hunter
[email protected]
Summary
During DNA double-strand-break (DSB) repair by recombination, the broken chromosome uses a homologous chromosome as a repair template. Early steps of recombination are well characterized: DSB ends assemble filaments of RecA-family proteins that catalyze homologous pairing and strand-invasion reactions. By contrast, the postinvasion steps of recombination are poorly characterized. Rad52 plays an essential role during early steps of recombination by mediating assembly of a RecA homolog, Rad51, into nucleoprotein filaments. The meiosis-specific RecA-homolog Dmc1 does not show this dependence, however. By exploiting the Rad52 independence of Dmc1, we reveal that Rad52 promotes postinvasion steps of both crossover and noncrossover pathways of meiotic recombination in Saccharomyces cerevisiae. This activity resides in the N-terminal region of Rad52, which can anneal complementary DNA strands, and is independent of its Rad51-assembly function. Our findings show that Rad52 functions in temporally and biochemically distinct reactions and suggest a general annealing mechanism for reuniting DSB ends during recombination.