Risky repair: DNA-protein crosslinks formed by mitochondrial base excision DNA repair enzymes acting on free radical lesions.
Risky repair: DNA-protein crosslinks formed by mitochondrial base excision DNA repair enzymes acting on free radical lesions.
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DOI：
10.1016/j.freeradbiomed.2016.11.025
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发表时间：
2017-06
影响因子：
7.4
通讯作者：
Demple B
中科院分区：
文献类型：
--
作者：
Caston RA;Demple B
氧气对于有氧细胞功能来说是必要的，也是危险的。ATP是最有效地由电子传递链，这需要氧作为电子受体。然而，氧气的存在，以及在某种程度上呼吸链本身，对细胞成分构成了危险。线粒体是氧化磷酸化的位点，具有防御和修复途径来科普氧化损伤。对于线粒体DNA，一个重要的途径是碱基切除修复，它作用于各种小的病变。然而，在某些情况下，尝试的DNA修复会导致更多的损伤，例如形成DNA-蛋白质交联，将修复酶捕获在DNA上。这是线粒体DNA聚合酶γ作用于在2-脱氧核糖的1-碳处氧化的脱碱基位点的情况。这样的DNA-蛋白质交联大概必须被去除，以恢复功能。在核DNA中，交联蛋白的泛素化和蛋白酶体的消化是必不可少的第一个加工步骤。这些机制如何以及是否对线粒体中的DNA-蛋白质交联起作用还有待观察。
Oxygen is both necessary and dangerous for the aerobic cell function. ATP is most efficiently made by the electron transport chain, which requires oxygen as an electron acceptor. However, the presence of oxygen, and to some extent the respiratory chain itself, poses a danger to cellular components. Mitochondria, the sites of oxidative phosphorylation, have defense and repair pathways to cope with oxidative damage. For mitochondrial DNA, an essential pathway is base excision repair, which acts on a variety of small lesions. There are instances, however, in which attempted DNA repair results in more damage, such as the formation of a DNA-protein crosslink trapping the repair enzyme on the DNA. That is the case for mitochondrial DNA polymerase γ acting on abasic sites oxidized at the 1-carbon of 2-deoxyribose. Such DNA-protein crosslinks presumably must be removed in order to restore function. In nuclear DNA, ubiquitylation of the crosslinked protein and digestion by the proteasome are essential first processing steps. How and whether such mechanisms operate on DNA-protein crosslinks in mitochondria remains to be seen.
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影响因子：
16
作者：
Bianchi, Julie;Rudd, Sean G.;Jozwiakowski, Stanislaw K.;Bailey, Laura J.;Soura, Violetta;Taylor, Elaine;Stevanovic, Irena;Green, Andrew J.;Stracker, Travis H.;Lindsay, Howard D.;Doherty, Aidan J.
通讯作者：
Doherty, Aidan J.
影响因子：
64.5
作者：
Duxin JP;Dewar JM;Yardimci H;Walter JC
通讯作者：
Walter JC
影响因子：
--
作者：
Finger, L David;Atack, John M;Shen, Binghui
通讯作者：
Shen, Binghui
影响因子：
14.9
作者：
Dianov GL;Hübscher U
通讯作者：
Hübscher U
DOI：
10.1073/pnas.062053799
发表时间：
2002-03-19
影响因子：
11.1
作者：
Hazra, TK;Izumi, T;Mitra, S
通讯作者：
Mitra, S