End-processing nucleases and phosphodiesterases: An elite supporting cast for the non-homologous end joining pathway of DNA double-strand break repair

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• 作者：Vijay Menon^a ; Lawrence F. Povirk^a ; ^b ; ^{lpovirk@vcu.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：DNA double-strand break repair ; End-processing ; Nucleases ; Phosphodiesterases
• 刊名：DNA Repair
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：43
• 期：Complete
• 页码：57-68
• 全文大小：2216 K

文摘

Nonhomologous end joining (NHEJ) is an error-prone DNA double-strand break repair pathway that is active throughout the cell cycle. A substantial fraction of NHEJ repair events show deletions and, less often, insertions in the repair joints, suggesting an end-processing step comprising the removal of mismatched or damaged nucleotides by nucleases and other phosphodiesterases, as well as subsequent strand extension by polymerases. A wide range of nucleases, including Artemis, Metnase, APLF, Mre11, CtIP, APE1, APE2 and WRN, are biochemically competent to carry out such double-strand break end processing, and have been implicated in NHEJ by at least circumstantial evidence. Several additional DNA end-specific phosphodiesterases, including TDP1, TDP2 and aprataxin are available to resolve various non-nucleotide moieties at DSB ends. This review summarizes the biochemical specificities of these enzymes and the evidence for their participation in the NHEJ pathway.