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裂殖酵母基因组中Rec12/Spo11强结合位点与减数分裂重组及着丝粒相关。

Sites of strong Rec12/Spo11 binding in the fission yeast genome are associated with meiotic recombination and with centromeres.

作者信息

Ludin Katja, Mata Juan, Watt Stephen, Lehmann Elisabeth, Bähler Jürg, Kohli Jürg

机构信息

Institute of Cell Biology, University of Bern, 3012 Bern, Switzerland.

出版信息

Chromosoma. 2008 Oct;117(5):431-44. doi: 10.1007/s00412-008-0159-3. Epub 2008 May 1.

Abstract

Meiotic recombination arises from Rec12/Spo11-dependent formation of DNA double-strand breaks (DSBs) and their subsequent repair. We identified Rec12-binding peaks across the Schizosaccharomyces pombe genome using chromatin immunoprecipitation after reversible formaldehyde cross-linking combined with whole-genome DNA microarrays. Strong Rec12 binding coincided with previously identified DSBs at the recombination hotspots ura4A, mbs1, and mbs2 and correlated with DSB formation at a new site. In addition, Rec12 binding corresponded to eight novel conversion hotspots and correlated with crossover density in segments of chromosome I. Notably, Rec12 binding inversely correlated with guanine-cytosine (GC) content, contrary to findings in Saccharomyces cerevisiae. Although both replication origins and Rec12-binding sites preferred AT-rich gene-free regions, they seemed to exclude each other. We also uncovered a connection between binding sites of Rec12 and meiotic cohesin Rec8. Rec12-binding peaks lay often within 2.5 kb of a Rec8-binding peak. Rec12 binding showed preference for large intergenic regions and was found to bind preferentially near to genes expressed strongly in meiosis. Surprisingly, Rec12 binding was also detected in centromeric core regions, which raises the intriguing possibility that Rec12 plays additional roles in meiotic chromosome dynamics.

摘要

减数分裂重组源于Rec12/Spo11依赖性DNA双链断裂(DSB)的形成及其后续修复。我们通过可逆甲醛交联后的染色质免疫沉淀结合全基因组DNA微阵列,鉴定了粟酒裂殖酵母基因组中的Rec12结合峰。强烈的Rec12结合与之前在重组热点ura4A、mbs1和mbs2处鉴定的DSB一致,并与一个新位点的DSB形成相关。此外,Rec12结合对应于八个新的转换热点,并与I号染色体片段中的交叉密度相关。值得注意的是,与酿酒酵母中的发现相反,Rec12结合与鸟嘌呤-胞嘧啶(GC)含量呈负相关。虽然复制起点和Rec12结合位点都偏好富含AT的无基因区域,但它们似乎相互排斥。我们还发现了Rec12和减数分裂黏连蛋白Rec8的结合位点之间的联系。Rec12结合峰通常位于Rec8结合峰的2.5 kb范围内。Rec12结合偏好于大的基因间区域,并且发现其优先结合在减数分裂中强烈表达的基因附近。令人惊讶的是,在着丝粒核心区域也检测到了Rec12结合,这增加了Rec12在减数分裂染色体动力学中发挥额外作用的有趣可能性。

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