Rap1通过非同源末端连接防止端粒融合。
Rap1 prevents telomere fusions by nonhomologous end joining.
作者信息
Pardo Benjamin, Marcand Stéphane
机构信息
Laboratoire de Radiobiologie de l'ADN, Service de Radiobiologie Moléculaire et Cellulaire, CEA/Fontenay, Fontenay aux Roses, France.
出版信息
EMBO J. 2005 Sep 7;24(17):3117-27. doi: 10.1038/sj.emboj.7600778. Epub 2005 Aug 11.
Abstract
Telomeres protect chromosomes from end-to-end fusions. In yeast Saccharomyces cerevisiae, the protein Rap1 directly binds telomeric DNA. Here, we use a new conditional allele of RAP1 and show that Rap1 loss results in frequent fusions between telomeres. Analysis of the fusion point with restriction enzymes indicates that fusions occur between telomeres of near wild-type length. Telomere fusions are not observed in cells lacking factors required for nonhomologous end joining (NHEJ), including Lig4 (ligase IV), KU and the Mre11 complex. SAE2 and TEL1 do not affect the frequency of fusions. Together, these results show that Rap1 is essential to block NHEJ between telomeres. Since the presence of Rap1 at telomeres has been conserved through evolution, the establishment of NHEJ suppression by Rap1 could be universal.
摘要
端粒保护染色体避免端对端融合。在酿酒酵母中，蛋白质Rap1直接结合端粒DNA。在此，我们使用一个新的RAP1条件等位基因，发现Rap1缺失会导致端粒间频繁融合。用限制酶分析融合点表明，融合发生在接近野生型长度的端粒之间。在缺乏非同源末端连接（NHEJ）所需因子（包括连接酶IV（Lig4）、KU和Mre11复合体）的细胞中未观察到端粒融合。SAE2和TEL1不影响融合频率。这些结果共同表明，Rap1对于阻止端粒间的NHEJ至关重要。由于Rap1在端粒处的存在在进化过程中一直得以保留，因此Rap1对NHEJ的抑制作用可能具有普遍性。
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2
Counting of Rif1p and Rif2p on Saccharomyces cerevisiae telomeres regulates telomere length.酿酒酵母端粒上Rif1p和Rif2p的计数调节端粒长度。
Mol Cell Biol. 2004 Dec;24(24):10857-67. doi: 10.1128/MCB.24.24.10857-10867.2004.
3
Homologous recombination generates T-loop-sized deletions at human telomeres.同源重组在人类端粒处产生T环大小的缺失。
Cell. 2004 Oct 29;119(3):355-68. doi: 10.1016/j.cell.2004.10.011.
4
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5
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