New paradigms in the repair of oxidative damage in human genome: mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins.
New paradigms in the repair of oxidative damage in human genome: mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins.
复制标题
修复人类基因组中氧化损伤的新范例：确保在复制和辅助蛋白参与期间修复诱变碱病变的机制。
DOI：
10.1007/s00018-014-1820-z
复制
发表时间：
2015-05
影响因子：
8
通讯作者：
Hegde, Muralidhar L.
中科院分区：
文献类型：
--
作者：
Dutta, Arijit;Yang, Chunying;Sengupta, Shiladitya;Mitra, Sankar;Hegde, Muralidhar L.
关键词：
哺乳动物基因组中的氧化碱基由于其错配性质而总是致突变的，其被内源性活性氧（ROS）持续诱导，并且在氧化应激后更丰富。与基因组中由UV和其他环境诱变剂诱导的阻断复制型DNA聚合酶的大体积碱基加合物不同，通过模板链中胞嘧啶的氧化脱氨基作用产生的氧化损伤碱基如5-羟基尿嘧啶（5-OHU）不阻断复制型聚合酶，因此需要在复制之前修复以防止突变。继我们早期的研究表明，Nei核酸内切酶VIII样1（NEIL 1）DNA糖基化酶，在哺乳动物细胞中的五个碱基切除修复（BER）启动酶之一，在S-期和复制叉模拟单链（SS）DNA底物的更高的亲和力增强的表达，我们最近提供了直接的实验证据NEIL 1的复制模板链修复的作用。我们将此事件命名为复制前BER的“捕牛者”机制，其关键要求是NEIL 1与ss DNA模板中的损伤碱基的非生产性结合（底物结合而无产物形成）以停止DNA合成，从而导致分叉退化。再退火双链体中损伤的修复然后由NEIL 1与DNA复制蛋白联合进行。NEIL 1（和其他BER起始酶）还与几种辅助和非典型蛋白相互作用，包括异质核核糖核蛋白U（hnRNP-U）和Y盒结合蛋白1（YB-1）以及高迁移率族蛋白1（HMGB 1），其在BER中的确切作用仍然不清楚。在这篇综述中，我们已经讨论了我们的理解的氧化基因组损伤修复途径的最新进展，特别关注复制前的模板链修复和支架因子的作用，如X射线修复交叉互补蛋白1（XRCC 1）和聚[ADP-核糖]聚合酶1（PARP 1）和其他辅助蛋白指导不同的BER子途径。
Oxidized bases in the mammalian genome, which are invariably mutagenic due to their mis-pairing property, are continuously induced by endogenous reactive oxygen species (ROS) and more abundantly after oxidative stress. Unlike bulky base adducts induced by UV and other environmental mutagens in the genome that block replicative DNA polymerases, oxidatively damaged bases such as 5-hydoxyuracil (5-OHU), produced by oxidative deamination of cytosine in the template strand, do not block replicative polymerases and thus need to be repaired prior to replication in order to prevent mutation. Following up our earlier studies, which showed that the Nei endonuclease VIII like 1 (NEIL1) DNA glycosylase, one of five base excision repair (BER)-initiating enzymes in mammalian cells, has enhanced expression during the S-phase and higher affinity for replication fork-mimicking single-stranded (ss) DNA substrates, we recently provided direct experimental evidence for NEIL1’s role in replicating template-strand repair. The key requirement for this event, which we named as the ‘cow-catcher’ mechanism of pre-replicative BER, is NEIL1’s non-productive binding (substrate binding without product formation) to the lesion base in ss DNA template to stall DNA synthesis, causing fork regression. Repair of the lesion in re-annealed duplex is then carried out by NEIL1 in association with the DNA replication proteins. NEIL1 (and other BER-initiating enzymes) also interact with several accessory and non-canonical proteins including the heterogeneous nuclear ribonucleoprotein U (hnRNP-U) and Y-box-binding protein 1 (YB-1) as well as high mobility group box 1 protein (HMGB1), whose precise roles in BER are still obscure. In this review, we have discussed the recent advances in our understanding of oxidative genome damage repair pathways with particular focus on the pre-replicative template strand repair and the role of scaffold factors like X-ray repair cross-complementing protein 1 (XRCC1) and Poly [ADP-ribose] polymerase 1 (PARP1) and other accessory proteins guiding distinct BER sub-pathways.
登录
查看更多内容
影响因子：
11.4
作者：
BOITEUX, S;OCONNOR, TR;LAVAL, J
通讯作者：
LAVAL, J
DOI：
10.1097/01.pgp.0000235064.93182.ec
发表时间：
2007-04-01
影响因子：
2.4
作者：
Brustmann, Hermann
通讯作者：
Brustmann, Hermann
影响因子：
4.8
作者：
Beernink, PT;Hwang, M;Thelen, MP
通讯作者：
Thelen, MP
影响因子：
4.3
作者：
Britton, Sebastien;Froment, Carine;Calsou, Patrick
通讯作者：
Calsou, Patrick
影响因子：
5.3
作者：
CALDECOTT, KW;MCKEOWN, CK;THOMPSON, LH
通讯作者：
THOMPSON, LH