Alternative end-joining pathway(s): Bricolage at DNA breaks

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• 作者：Philippe Frit^a ; ^b ; ^c ; Nadia Barboule^a ; ^b ; ^c ; Ying Yuan^a ; ^b ; ^c ; Dennis Gomez^a ; ^b ; ^c ; Patrick Calsou^a ; ^b ; ^c ; ^{calsou@ipbs.fr" class="auth_mail}
• 关键词：DNA repair ; Non-homologous endjoining (NHEJ) ; DNA double-strand breaks (DSBs) ; V(D)J Recombination ; Class-switch recombination ; Telomere
• 刊名：DNA Repair
• 出版年：May 2014
• 年：2014
• 卷：17
• 期：Complete
• 页码：81-97
• 全文大小：3467 K

文摘

To cope with DNA double strand break (DSB) genotoxicity, cells have evolved two main repair pathways: homologous recombination which uses homologous DNA sequences as repair templates, and non-homologous Ku-dependent end-joining involving direct sealing of DSB ends by DNA ligase IV (Lig4). During the last two decades a third player most commonly named alternative end-joining (A-EJ) has emerged, which is defined as any Ku- or Lig4-independent end-joining process. A-EJ increasingly appears as a highly error-prone bricolage on DSBs and despite expanding exploration, it still escapes full characterization. In the present review, we discuss the mechanism and regulation of A-EJ as well as its biological relevance under physiological and pathological situations, with a particular emphasis on chromosomal instability and cancer. Whether or not it is a genuine DSB repair pathway, A-EJ is emerging as an important cellular process and understanding A-EJ will certainly be a major challenge for the coming years.