Mitochondrial DNA damage and its consequences for mitochondrial gene expression.
Mitochondrial DNA damage and its consequences for mitochondrial gene expression.
复制标题
DOI：
10.1016/j.bbagrm.2012.06.002
复制
发表时间：
2012-09
影响因子：
4.7
通讯作者：
Cline, Susan D.
中科院分区：
文献类型：
--
作者：
Cline, Susan D.
关键词：
线粒体如何处理DNA损伤，以及线粒体DNA损伤（mtDNA）稳态水平的变化是否有助于线粒体功能障碍，这些问题推动了衰老和疾病发病机制研究领域的蓬勃发展。在过去的十年中，研究人员已经确定和测量了各种形式的内源性和环境mtDNA损伤，并阐明了mtDNA修复途径。有趣的是，线粒体似乎并不包含在细胞核中运作的全部DNA修复机制，尽管mtDNA包含作为每个细胞核DNA修复途径靶点的损伤类型。修复能力的降低可以部分解释线粒体染色体的高突变频率。由于mtDNA复制依赖于转录，mtDNA损伤可在三个水平上改变线粒体基因表达：通过引起DNA聚合酶γ核苷酸掺入错误导致突变，通过干扰线粒体RNA聚合酶对mtDNA复制的启动，或通过诱导转录突变或过早的转录终止。本文综述了线粒体DNA损伤、修复及其对线粒体DNA完整性和基因表达的影响。
How mitochondria process DNA damage and whether a change in the steady-state level of mitochondrial DNA damage (mtDNA) contributes to mitochondrial dysfunction are questions that fuel burgeoning areas of research into aging and disease pathogenesis. Over the past decade, researchers have identified and measured various forms of endogenous and environmental mtDNA damage and have elucidated mtDNA repair pathways. Interestingly, mitochondria do not appear to contain the full range of DNA repair mechanisms that operate in the nucleus, although mtDNA contains types of damage that are targets of each nuclear DNA repair pathway. The reduced repair capacity may, in part, explain the high mutation frequency of the mitochondrial chromosome. Since mtDNA replication is dependent on transcription, mtDNA damage may alter mitochondrial gene expression at three levels: by causing DNA polymerase γ nucleotide incorporation errors leading to mutations, by interfering with the priming of mtDNA replication by the mitochondrial RNA polymerase, or by inducing transcriptional mutagenesis or premature transcript termination. This review summarizes our current knowledge of mtDNA damage, its repair, and its effects on mtDNA integrity and gene expression.
登录
查看更多内容
影响因子：
14.9
作者：
Cline SD;Lodeiro MF;Marnett LJ;Cameron CE;Arnold JJ
通讯作者：
Arnold JJ
影响因子：
4.8
作者：
Aamann, Maria D.;Sorensen, Martin M.;Bohr, Vilhelm A.
通讯作者：
Bohr, Vilhelm A.
影响因子：
4.8
作者：
Ayala-Torres, S;Chen, YM;Van Houten, B
通讯作者：
Van Houten, B
影响因子：
56.9
作者：
BACKER, JM;WEINSTEIN, IB
通讯作者：
WEINSTEIN, IB
影响因子：
3.9
作者：
Brand, Martin D.
通讯作者：
Brand, Martin D.