A mobile threat to genome stability: The impact of non-LTR retrotransposons upon the human genome.
A mobile threat to genome stability: The impact of non-LTR retrotransposons upon the human genome.
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DOI：
10.1016/j.semcancer.2010.03.001
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发表时间：
2010-08
影响因子：
14.5
通讯作者：
Batzer MA
中科院分区：
文献类型：
--
作者：
Konkel MK;Batzer MA
现在人们普遍认为，人类基因组并不是最初假定的稳定实体。缺失、重复、倒位和插入是常见的，并且对基因组结构变异（SV）有显著贡献。它们的集体影响产生了在人类中观察到的个体间基因组多样性。这些变异不仅改变了基因组的结构;它们还可能具有功能性影响，例如改变基因表达。一些SV已被确定为遗传疾病的原因，包括癌症易感性。癌细胞因其基因组不稳定性而臭名昭著，并且经常在转座因子（TE）促成的微观和亚微观水平上显示基因组重排。在这里，我们回顾了TE在基因组不稳定性中的作用，特别关注非LTR反转录转座子。目前，三个非LTR反转录转座子家族-长散布元件1（L1）、SVA（短散布元件（SINE-R）、可变数目串联重复（VNTR）和Alu（a SINE）元件-在人类基因组中移动，并通过基于插入和基于插入后的诱变引起基因组不稳定性。由于TE的丰度和高序列同一性，它们经常将同源重组修复途径误导为非等位基因同源重组，导致缺失、重复和倒位。虽然研究较少，但非LTR反转录转座子插入和TE介导的重排在癌细胞中可能比在健康组织中更常见。这可能至少部分归因于常见的整体低甲基化以及癌细胞的一般表观遗传功能障碍。在可能的情况下，我们提供影响癌症易感性和/或发展的例子。
It is now commonly agreed that the human genome is not the stable entity originally presumed. Deletions, duplications, inversions, and insertions are common, and contribute significantly to genomic structural variations (SVs). Their collective impact generates much of the inter-individual genomic diversity observed among humans. Not only do these variations change the structure of the genome; they may also have functional implications, e.g. altered gene expression. Some SVs have been identified as the cause of genetic disorders, including cancer predisposition. Cancer cells are notorious for their genomic instability, and often show genomic rearrangements at the microscopic and submicroscopic level to which transposable elements (TEs) contribute. Here, we review the role of TEs in genome instability, with particular focus on non-LTR retrotransposons. Currently, three non-LTR retrotransposon families – long interspersed element 1 (L1), SVA (short interspersed element (SINE-R), variable number of tandem repeats (VNTR), and Alu), and Alu (a SINE) elements – mobilize in the human genome, and cause genomic instability through both insertion- and post-insertion-based mutagenesis. Due to the abundance and high sequence identity of TEs, they frequently mislead the homologous recombination repair pathway into non-allelic homologous recombination, causing deletions, duplications, and inversions. While less comprehensively studied, non-LTR retrotransposon insertions and TE-mediated rearrangements are probably more common in cancer cells than in healthy tissue. This may be at least partially attributed to the commonly seen global hypomethylation as well as general epigenetic dysfunction of cancer cells. Where possible, we provide examples that impact cancer predisposition and/or development.
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DOI：
10.1073/pnas.0831042100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Brouha, B;Schustak, J;Kazazian, HH
通讯作者：
Kazazian, HH
影响因子：
4
作者：
Cybulski, C.;Wokolorczyk, D.;Lubinski, J.
通讯作者：
Lubinski, J.
影响因子：
4
作者：
Casarin, Alberto;Martella, Maddalena;Murgia, Alessandra
通讯作者：
Murgia, Alessandra
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.5
作者：
Cordaux, Richard;Lee, Jungnam;Batzer, Mark A.
通讯作者：
Batzer, Mark A.