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低水平DNA聚合酶诱导酵母中的染色体易位:染色体脆弱位点的一个模型

Chromosomal translocations in yeast induced by low levels of DNA polymerase a model for chromosome fragile sites.

作者信息

Lemoine Francene J, Degtyareva Natasha P, Lobachev Kirill, Petes Thomas D

机构信息

Department of Biology and Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

出版信息

Cell. 2005 Mar 11;120(5):587-98. doi: 10.1016/j.cell.2004.12.039.

DOI:10.1016/j.cell.2004.12.039
PMID:15766523
Abstract

In the yeast Saccharomyces cerevisiae, reduced levels of the replicative alpha DNA polymerase result in greatly elevated frequencies of chromosome translocations and chromosome loss. We selected translocations in a small region of chromosome III and found that they involve homologous recombination events between yeast retrotransposons (Ty elements) on chromosome III and retrotransposons located on other chromosomes. One of the two preferred sites of these translocations on chromosome III involve two Ty elements arrayed head-to-head; disruption of this site substantially reduces the rate of translocations. We demonstrate that this pair of Ty elements constitutes a preferred site for double-strand DNA breaks when DNA replication is compromised, analogous to the fragile sites observed in mammalian chromosomes.

摘要

在酿酒酵母中,复制性α DNA聚合酶水平降低会导致染色体易位和染色体丢失的频率大幅升高。我们在第三条染色体的一个小区域内选择了易位事件,发现它们涉及第三条染色体上的酵母逆转录转座子(Ty元件)与位于其他染色体上的逆转录转座子之间的同源重组事件。这些易位在第三条染色体上的两个优先位点之一涉及两个首尾相连排列的Ty元件;破坏这个位点会大幅降低易位率。我们证明,当DNA复制受损时,这对Ty元件构成双链DNA断裂的优先位点,类似于在哺乳动物染色体中观察到的脆性位点。

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Chromosomal translocations in yeast induced by low levels of DNA polymerase a model for chromosome fragile sites.低水平DNA聚合酶诱导酵母中的染色体易位:染色体脆弱位点的一个模型
Cell. 2005 Mar 11;120(5):587-98. doi: 10.1016/j.cell.2004.12.039.
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Reduced replication: a call to ARMS.复制减少:对ARMS的呼吁。
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Recombination between retrotransposons as a source of chromosome rearrangements in the yeast Saccharomyces cerevisiae.逆转座子之间的重组作为酿酒酵母染色体重排的一个来源。
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Cycles of chromosome instability are associated with a fragile site and are increased by defects in DNA replication and checkpoint controls in yeast.染色体不稳定周期与一个脆性位点相关,并且在酵母中因DNA复制缺陷和检查点控制缺陷而增加。
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Capture of retrotransposon DNA at the sites of chromosomal double-strand breaks.在染色体双链断裂位点捕获逆转录转座子DNA。
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Frequent chromosomal translocations induced by DNA double-strand breaks.由DNA双链断裂诱导的频繁染色体易位。
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Chromosome aberrations resulting from double-strand DNA breaks at a naturally occurring yeast fragile site composed of inverted ty elements are independent of Mre11p and Sae2p.由组成自然发生的酵母脆性位点的反向 ty 元件的双链 DNA 断裂引起的染色体畸变与 Mre11p 和 Sae2p 无关。
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Loss of DNA polymerase zeta causes chromosomal instability in mammalian cells.DNA聚合酶ζ的缺失会导致哺乳动物细胞中的染色体不稳定。
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