Sir2p suppresses recombination of replication forks stalled at the replication fork barrier of ribosomal DNA in Saccharomyces cerevisiae
Sir2p suppresses recombination of replication forks stalled at the replication fork barrier of ribosomal DNA in Saccharomyces cerevisiae
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DOI：
10.1093/nar/gkg188
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发表时间：
2003-02-01
影响因子：
14.9
通讯作者：
Schvartzman, JB
中科院分区：
文献类型：
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作者：
Benguría, A;Hernández, P;Schvartzman, JB
在酿酒酵母的核糖体 DNA (rDNA) 中，复制叉在位于 35S 转录单元附近和下游的极性复制叉屏障 (RFB) 处逆着转录停滞进行。在此屏障处受阻的分叉具有潜在的重组性。在 Sir2 突变细胞中，携带 RFB 序列的质粒以其活性方向整合到染色体 rDNA 中，但在野生型细胞中则不然，这表明组蛋白脱乙酰酶沉默蛋白 Sir2 (Sir2p) 也调节酵母的衰老过程，抑制在 rDNA RFB 处阻断的叉的重组能力。 RFB序列在其非活性过程中的定向或通过FOB1删除而消除的定向避免了sir2突变细胞中的质粒整合，这表明在质粒环境中叉的停滞是重组发生所必需的。总而言之，这些结果强烈表明 Sir2p 的功能之一是调节重组机制对停滞在 rDNA RFB 处的叉的访问。
In the ribosomal DNA (rDNA) of Saccharomyces cerevisiae replication forks progressing against transcription stall at a polar replication fork barrier (RFB) located close to and downstream of the 35S transcription unit. Forks blocked at this barrier are potentially recombinogenic. Plasmids bearing the RFB sequence in its active orientation integrated into the chromosomal rDNA in sir2 mutant cells but not in wild-type cells, indicating that the histone deacetylase silencing protein Sir2 (Sir2p), which also modulates the aging process in yeast, suppresses the recombination competence of forks blocked at the rDNA RFB. Orientation of the RFB sequence in its inactive course or its abolition by FOB1 deletion avoided plasmid integration in sir2 mutant cells, indicating that stalling of the forks in the plasmid context was required for recombination to take place. Altogether these results strongly suggest that one of the functions of Sir2p is to modulate access of the recombination machinery to the forks stalled at the rDNA RFB.