Mechanisms of interstrand DNA crosslink repair and human disorders.
Mechanisms of interstrand DNA crosslink repair and human disorders.
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DOI：
10.1186/s41021-016-0037-9
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Hanada K
中科院分区：
文献类型：
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作者：
Hashimoto S;Anai H;Hanada K
DNA 链间交联 (ICL) 是 DNA 沃森-克里克链之间通过共价键的连接，可防止 DNA 链分离。由于 ICL 损伤影响 DNA 的两条链，因此 ICL 修复并不简单。到目前为止，核苷酸切除修复 (NER)、结构特异性核酸内切酶、跨损伤 DNA 合成 (TLS)、同源重组 (HR) 和导致范可尼贫血 (FA) 的因子被确定参与 ICL 修复。由于 ICL 损伤的存在会导致转录和 DNA 复制的严重缺陷，这些 DNA 修复途径的突变会导致各种遗传性疾病。 NER对静止细胞中ICL的识别和清除起着重要作用，NER缺陷会导致先天性早衰综合征，如着色性干皮病、科凯恩综合征和毛发硫营养不良症。另一方面，S期的ICL修复需要更复杂的多种因素的协调，包括结构特异性核酸内切酶、TLS和HR。 S 期的 ICL 修复编排受到干扰会导致基因组不稳定，从而导致癌症易发疾病——范可尼贫血。迄今为止，ICL 修复中的 30 多个因素已被确定。最近，一种新的因子 UHRF1 被发现可以作为 ICL 的传感器。除此之外，还鉴定了参与 ICL 病变第一个切口（也称为脱钩）的核酸酶数量。在此，我们总结了近年来 ICL 相关疾病和修复机制的研究，重点是 ICL 的首次切口。
Interstrand DNA crosslinks (ICLs) are the link between Watson-Crick strands of DNAs with the covalent bond and prevent separation of DNA strands. Since the ICL lesion affects both strands of the DNA, the ICL repair is not simple. So far, nucleotide excision repair (NER), structure-specific endonucleases, translesion DNA synthesis (TLS), homologous recombination (HR), and factors responsible for Fanconi anemia (FA) are identified to be involved in ICL repair. Since the presence of ICL lesions causes severe defects in transcription and DNA replication, mutations in these DNA repair pathways give rise to a various hereditary disorders. NER plays an important role for the ICL recognition and removal in quiescent cells, and defects of NER causes congential progeria syndrome, such as xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. On the other hand, the ICL repair in S phase requires more complicated orchestration of multiple factors, including structure-specific endonucleases, and TLS, and HR. Disturbed this ICL repair orchestration in S phase causes genome instability resulting a cancer prone disease, Fanconi anemia. So far more than 30 factors in ICL repair have already identified. Recently, a new factor, UHRF1, was discovered as a sensor of ICLs. In addition to this, numbers of nucleases that are involved in the first incision, also called unhooking, of ICL lesions have also been identified. Here we summarize the recent studies of ICL associated disorders and repair mechanism, with emphasis in the first incision of ICLs.