Repair Pathway Choices and Consequences at the Double-Strand Break

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• 作者：Raphael Ceccaldi¹ ; Beatrice Rondinelli¹ ; Alan D. D&rsquo ; Andrea¹ ; ^{alan_dandrea@dfci.harvard.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：DNA repair ; homologous recombination ; alternative end joining ; Polθ ; synthetic lethality
• 刊名：Trends in Cell Biology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：26
• 期：1
• 页码：52-64
• 全文大小：2080 K

文摘

DNA double-strand breaks (DSBs) are cytotoxic lesions that threaten genomic integrity. Failure to repair a DSB has deleterious consequences, including genomic instability and cell death. Indeed, misrepair of DSBs can lead to inappropriate end-joining events, which commonly underlie oncogenic transformation due to chromosomal translocations. Typically, cells employ two main mechanisms to repair DSBs: homologous recombination (HR) and classical nonhomologous end joining (C-NHEJ). In addition, alternative error-prone DSB repair pathways, namely alternative end joining (alt-EJ) and single-strand annealing (SSA), have been recently shown to operate in many different conditions and to contribute to genome rearrangements and oncogenic transformation. Here, we review the mechanisms regulating DSB repair pathway choice, together with the potential interconnections between HR and the annealing-dependent error-prone DSB repair pathways.