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DNA聚合酶δ在同源重组过程中被优先招募,以促进异源双链DNA的延伸。

DNA polymerase delta is preferentially recruited during homologous recombination to promote heteroduplex DNA extension.

作者信息

Maloisel Laurent, Fabre Francis, Gangloff Serge

机构信息

CEA, DSV, iRCM, SIGRR, LERA, Fontenay-aux-Roses F-92265, France.

出版信息

Mol Cell Biol. 2008 Feb;28(4):1373-82. doi: 10.1128/MCB.01651-07. Epub 2007 Dec 17.


DOI:10.1128/MCB.01651-07
PMID:18086882
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2258756/
Abstract

DNA polymerases play a central role during homologous recombination (HR), but the identity of the enzyme(s) implicated remains elusive. The pol3-ct allele of the gene encoding the catalytic subunit of DNA polymerase delta (Poldelta) has highlighted a role for this polymerase in meiotic HR. We now address the ubiquitous role of Poldelta during HR in somatic cells. We find that pol3-ct affects gene conversion tract length during mitotic recombination whether the event is initiated by single-strand gaps following UV irradiation or by site-specific double-strand breaks. We show that the pol3-ct effects on gene conversion are completely independent of mismatch repair, indicating that shorter gene conversion tracts in pol3-ct correspond to shorter extensions of primed DNA synthesis. Interestingly, we find that shorter repair tracts do not favor synthesis-dependent strand annealing at the expense of double-strand-break repair. Finally, we show that the DNA polymerases that have been previously suspected to mediate HR repair synthesis (Polepsilon and Poleta) do not affect gene conversion during induced HR, including in the pol3-ct background. Our results argue strongly for the preferential recruitment of Poldelta during HR.

摘要

DNA聚合酶在同源重组(HR)过程中发挥核心作用,但涉及的具体酶的身份仍不清楚。编码DNA聚合酶δ(Poldelta)催化亚基的基因的pol3-ct等位基因突出了该聚合酶在减数分裂HR中的作用。我们现在探讨Poldelta在体细胞HR中的普遍作用。我们发现,无论该事件是由紫外线照射后的单链缺口引发还是由位点特异性双链断裂引发,pol3-ct都会影响有丝分裂重组过程中的基因转换片段长度。我们表明,pol3-ct对基因转换的影响完全独立于错配修复,这表明pol3-ct中较短的基因转换片段对应于引发的DNA合成的较短延伸。有趣的是,我们发现较短的修复片段并不利于以双链断裂修复为代价的合成依赖性链退火。最后,我们表明,先前怀疑介导HR修复合成的DNA聚合酶(Polepsilon和Poleta)在诱导的HR过程中不影响基因转换,包括在pol3-ct背景下。我们的结果有力地支持了HR过程中Poldelta的优先募集。

相似文献

[1]
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本文引用的文献

[1]
Meiotic recombination-related DNA synthesis and its implications for cross-over and non-cross-over recombinant formation.

Proc Natl Acad Sci U S A. 2007-4-3

[2]
The role of DNA double-strand breaks in spontaneous homologous recombination in S. cerevisiae.

PLoS Genet. 2006-11-10

[3]
Conservative inheritance of newly synthesized DNA in double-strand break-induced gene conversion.

Mol Cell Biol. 2006-12

[4]
Crossover homeostasis in yeast meiosis.

Cell. 2006-7-28

[5]
Mrc1 and Srs2 are major actors in the regulation of spontaneous crossover.

EMBO J. 2006-6-21

[6]
Sgs1 regulates gene conversion tract lengths and crossovers independently of its helicase activity.

Mol Cell Biol. 2006-6

[7]
Analysis of the proteins involved in the in vivo repair of base-base mismatches and four-base loops formed during meiotic recombination in the yeast Saccharomyces cerevisiae.

Genetics. 2006-7

[8]
Dual roles for DNA polymerase eta in homologous DNA recombination and translesion DNA synthesis.

Mol Cell. 2005-12-9

[9]
Human DNA polymerase eta promotes DNA synthesis from strand invasion intermediates of homologous recombination.

Mol Cell. 2005-12-9

[10]
Crosstalk between SUMO and ubiquitin on PCNA is mediated by recruitment of the helicase Srs2p.

Mol Cell. 2005-7-1

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