Fanconi anemia-independent DNA inter-strand crosslink repair in eukaryotes.

Fanconi anemia-independent DNA inter-strand crosslink repair in eukaryotes.
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DOI:
10.1016/j.pbiomolbio.2020.08.005
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发表时间:
2020-12
影响因子:
3.8
通讯作者:
Bochman ML
Bochman ML
中科院分区:
生物学3区
文献类型:
--
作者:
Rogers CM;Simmons Iii RH;Fluhler Thornburg GE;Buehler NJ;Bochman ML

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DNA链间交联(ICL)是一种危险的损伤,可由多种内源性和外源性双功能化合物引起。由于共价连接双螺旋的两条链局部破坏DNA复制和转录,因此即使不能去除单个ICL也可能对细胞致命。因此,多种ICL修复途径已经发展,其中研究最多的是经典范可尼贫血(FA)途径。然而,最近的研究表明,不同类型的ICL(例如,骨架扭曲与非扭曲)的差异,然后细胞使用FA途径或多种FA非依赖性ICL修复途径之一产生特异性修复应答。本文综述的重点是后者,包括目前的工作,转录耦合,碱基切除,乙酰丙酮诱导,SNM 1A/RecQ 4 ICL修复途径,并强调在该领域未回答的问题。阐明这些问题将为ICL修复的各种途径提供机制上的见解,并使ICL诱导剂能够更有效地用作化疗药物。
DNA inter-strand crosslinks (ICLs) are dangerous lesions that can be caused by a variety of endogenous and exogenous bifunctional compounds. Because covalently linking both strands of the double helix locally disrupts DNA replication and transcription, failure to remove even a single ICL can be fatal to the cell. Thus, multiple ICL repair pathways have evolved, with the best studied being the canonical Fanconi anemia (FA) pathway. However, recent research demonstrates that different types of ICLs (e.g., backbone distorting vs. non-distorting) can be discriminated by the cell, which then mounts a specific repair response using the FA pathway or one of a variety of FA-independent ICL repair pathways. This review focuses on the latter, covering current work on the transcription-coupled, base excision, acetaldehyde-induced, and SNM1A/RecQ4 ICL repair pathways and highlighting unanswered questions in the field. Answering these questions will provide mechanistic insight into the various pathways of ICL repair and enable ICL-inducing agents to be more effectively used as chemotherapeutics.
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