Reduced levels of DNA polymerase δ induce chromosome fragile site instability in yeast
Reduced levels of DNA polymerase δ induce chromosome fragile site instability in yeast
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DOI：
10.1128/mcb.02084-07
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发表时间：
2008-09-01
影响因子：
5.3
通讯作者：
Petes, Thomas D.
中科院分区：
文献类型：
--
作者：
Lemoine, Francene J.;Degtyareva, Natasha P.;Petes, Thomas D.
基因组的特定区域（脆性位点）是与许多类型的癌细胞相关的染色体重排的热点。因此，了解调控染色体脆性位点稳定性的分子机制在癌症生物学中具有重要意义。我们以前确定了两个染色体脆性位点在酿酒酵母中诱导的Pol1p，DNA聚合酶α的催化亚基的表达减少。在这里提出的研究中，我们表明，Pol3p，DNA聚合酶δ的催化亚基的水平降低，诱导在这些相同的网站不稳定，并导致产生各种染色体畸变。这些发现表明，复制DNA聚合酶化学计量的变化会导致重组DNA损伤，可能是双链DNA断裂。
Specific regions of genomes (fragile sites) are hot spots for the chromosome rearrangements that are associated with many types of cancer cells. Understanding the molecular mechanisms regulating the stability of chromosome fragile sites, therefore, has important implications in cancer biology. We previously identified two chromosome fragile sites in Saccharomyces cerevisiae that were induced in response to the reduced expression of Pol1p, the catalytic subunit of DNA polymerase alpha. In the study presented here, we show that reduced levels of Pol3p, the catalytic subunit of DNA polymerase delta, induce instability at these same sites and lead to the generation of a variety of chromosomal aberrations. These findings demonstrate that a change in the stoichiometry of replicative DNA polymerases results in recombinogenic DNA lesions, presumably double-strand DNA breaks.