Gross chromosomal rearrangements and elevated recombination at an inducible site-specific replication fork barrier

被引:215
作者
Lambert, S [1 ]
Watson, A [1 ]
Sheedy, DM [1 ]
Martin, B [1 ]
Carr, AM [1 ]
机构
[1] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England
基金
英国医学研究理事会;
关键词
D O I
10.1016/j.cell.2005.03.022
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
Genomic rearrangements linked to aberrant recombination are associated with cancer and human genetic diseases. Such recombination has indirectly been linked to replication fork stalling. Using fission yeast, we have developed a genetic system to block replication forks at nonhistone/DNA complexes located at a specific euchromatic site. We demonstrate that stalled replication forks lead to elevated intrachromosomal and ectopic recombination promoting site-specific gross chromosomal rearrangements. We show that recombination is required to promote cell viability when forks are stalled, that recombination proteins associate with sites of fork stalling, and that recombination participates in deleterious site-specific chromosomal rearrangements. Thus, recombination is a "double-edged sword," preventing cell death when the replisome disassembles at the expense of genetic stability.
引用
收藏
页码:689 / 702
页数:14
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