Rad52's DNA annealing activity drives template switching associated with restarted DNA replication.
Rad52's DNA annealing activity drives template switching associated with restarted DNA replication.
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DOI：
10.1038/s41467-022-35060-4
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发表时间：
2022-11-26
影响因子：
16.6
通讯作者：
Whitby, Matthew C.
中科院分区：
文献类型：
--
作者：
Kishkevich, Anastasiya;Tamang, Sanjeeta;Nguyen, Michael O.;Oehler, Judith;Bulmaga, Elena;Andreadis, Christos;Morrow, Carl A.;Osman, Fekret;Whitby, Matthew C.
据认为，许多与先天性疾病和癌症相关的简单和复杂的基因组重排源于重组酶重新启动折叠的复制叉期间所犯的错误。据推测，这种重组介导的重启过程从相对准确的起始阶段过渡到不太准确的延伸阶段，其特征在于同源、同源和微同源DNA序列之间的广泛模板转换。使用一个实验系统在裂变酵母，叉崩溃是由一个位点特异性复制障碍触发，我们表明，异位重组，与重组依赖性复制（RDR）的启动，主要是由Rad51重组酶驱动，而模板切换，在RDR的延伸阶段，更多地依赖于DNA退火Rad52。这一发现为过渡假说提供了证据和机制基础。折叠的复制叉的重新启动与基因组重排的高速率相关。在这里，作者表明，在重新启动启动期间，重排主要由Rad51驱动，而在延伸期间，它们更多地依赖于Rad52。
It is thought that many of the simple and complex genomic rearrangements associated with congenital diseases and cancers stem from mistakes made during the restart of collapsed replication forks by recombination enzymes. It is hypothesised that this recombination-mediated restart process transitions from a relatively accurate initiation phase to a less accurate elongation phase characterised by extensive template switching between homologous, homeologous and microhomologous DNA sequences. Using an experimental system in fission yeast, where fork collapse is triggered by a site-specific replication barrier, we show that ectopic recombination, associated with the initiation of recombination-dependent replication (RDR), is driven mainly by the Rad51 recombinase, whereas template switching, during the elongation phase of RDR, relies more on DNA annealing by Rad52. This finding provides both evidence and a mechanistic basis for the transition hypothesis. The restart of collapsed replication forks is associated with high rates of genomic rearrangement. Here, the authors show that during restart initiation rearrangements are driven mainly by Rad51, whereas during elongation they rely more on Rad52.
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影响因子：
64.5
作者：
Crickard, J. Brooks;Moevus, Corentin J.;Greene, Eric C.
通讯作者：
Greene, Eric C.
影响因子：
3.8
作者：
Cortez D
通讯作者：
Cortez D
DOI：
10.1126/science.1219379
发表时间：
2012-09-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
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通讯作者：
Bishop DK
影响因子：
3.5
作者：
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通讯作者：
Lupski, James R.
影响因子：
16.8
作者：
Haruta, Nami;Kurokawa, Yumiko;Iwasaki, Hiroshi
通讯作者：
Iwasaki, Hiroshi