Replication protein A prevents promiscuous annealing between short sequence homologies: Implications for genome integrity.

Replication protein A prevents promiscuous annealing between short sequence homologies: Implications for genome integrity.
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DOI:
10.1002/bies.201400161
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发表时间:
2015-03
期刊:
影响因子:
4
通讯作者:
Symington, Lorraine S.
Symington, Lorraine S.
中科院分区:
生物学3区
文献类型:
--
作者:
Deng, Sarah K.;Chen, Huan;Symington, Lorraine S.

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复制蛋白 A (RPA) 是主要的真核单链 DNA (ssDNA) 结合蛋白,在所有涉及 ssDNA 的 DNA 代谢反应中发挥重要作用。 RPA 以高亲和力结合 ssDNA,从而阻止二级结构的形成并保护 ssDNA 免受核酸酶的作用,并直接与其他 DNA 加工蛋白相互作用。在这里,我们讨论支持以下观点的最新结果:RPA 的一个功能是防止短重复之间的退火,这种退火可能通过微同源介导的末端连接或作为结构选择性核酸酶底物的发夹结构的形成而导致染色体重排。我们认为,RPA 耗尽引起的复制叉灾难可能是由核酸酶切割二级结构造成的,而无法切割 DNA 末端形成的发夹结构可能会导致基因扩增。这些研究强调了 RPA 在维持基因组完整性方面发挥的重要作用。
Replication protein A (RPA) is the main eukaryotic single-stranded DNA (ssDNA) binding protein, having essential roles in all DNA metabolic reactions involving ssDNA. RPA binds ssDNA with high affinity, thereby preventing the formation of secondary structures and protecting ssDNA from the action of nucleases, and directly interacts with other DNA processing proteins. Here we discuss recent results supporting the idea that one function of RPA is to prevent annealing between short repeats that can lead to chromosome rearrangements by microhomology-mediated end joining or the formation of hairpin structures that are substrates for structure-selective nucleases. We suggest that replication fork catastrophe caused by depletion of RPA could result from cleavage of secondary structures by nucleases, and that failure to cleave hairpin structures formed at DNA ends could lead to gene amplification. These studies highlight the important role RPA plays in maintaining genome integrity.
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