Short Inverted Repeats Are Hotspots for Genetic Instability: Relevance to Cancer Genomes.
Short Inverted Repeats Are Hotspots for Genetic Instability: Relevance to Cancer Genomes.
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DOI：
10.1016/j.celrep.2015.02.039
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发表时间：
2015-03-17
期刊：
影响因子：
8.8
通讯作者：
Vasquez KM
中科院分区：
文献类型：
--
作者：
Lu S;Wang G;Bacolla A;Zhao J;Spitser S;Vasquez KM
对人类遗传性疾病中染色体畸变的分析表明，反向重复序列（IR）通常与内源性染色体不稳定性和断裂热点共定位。人类基因组中大约 80% 的 IR 都很短（<100 bp），但这种短十字形形成序列的诱变潜力尚未得到表征。在这里，我们发现短IR在人类癌症的易位断点处富集，并刺激哺乳动物和酵母细胞中DNA双链断裂（DSB）和缺失的形成。我们为 IR 诱导的遗传不稳定性的复制相关机制和独立于 DNA 复制的新型 XPF 裂解机制提供了证据。这些新发现表明短IR是疾病病因学中DNA断裂的内源性来源，并表明这些重复代表了基因组可塑性的一个特征，可能通过提供群体内多样性的手段来促进人类基因组的进化。
Analyses of chromosomal aberrations in human genetic disorders have revealed that inverted repeat sequences (IRs) often co-localize with endogenous chromosomal instability and breakage hotspots. Approximately 80% of all IRs in the human genome are short (<100 bp), yet the mutagenic potential of such short cruciform-forming sequences has not been characterized. Here, we found that short IRs are enriched at translocation breakpoints in human cancer, and stimulate the formation of DNA double-strand breaks (DSBs) and deletions in mammalian and yeast cells. We provide evidence for replication-related mechanisms of IR-induced genetic instability and a novel XPF cleavage-based mechanism independent of DNA replication. These new discoveries implicate short IRs as endogenous sources of DNA breakage involved in disease etiology, and suggest that these repeats represent a feature of genome plasticity that may contribute to the evolution of the human genome by providing a means for diversity within the population.
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DOI：
10.1016/j.tig.2008.08.007
发表时间：
2008-11
期刊：
Trends in genetics : TIG
影响因子：
--
作者：
McVey M;Lee SE
通讯作者：
Lee SE
SLX1和MUS81-EME1核酸酶对Holliday连接分辨率和DNA修复的合作控制。
影响因子：
16
作者：
Castor, Dennis;Nair, Nidhi;Declais, Anne-Cecile;Lachaud, Christophe;Toth, Rachel;Macartney, Thomas J.;Lilley, David M. J.;Arthur, J. Simon C.;Rouse, John
通讯作者：
Rouse, John
影响因子：
4.5
作者：
Agostinho A;Meier B;Sonneville R;Jagut M;Woglar A;Blow J;Jantsch V;Gartner A
通讯作者：
Gartner A
DOI：
10.1073/pnas.1014240108
发表时间：
2011-03-22
影响因子：
11.1
作者：
Mankouri, Hocine W.;Ashton, Thomas M.;Hickson, Ian D.
通讯作者：
Hickson, Ian D.
影响因子：
64.5
作者：
Lambert, S;Watson, A;Carr, AM
通讯作者：
Carr, AM