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HMCES Maintains Genome Integrity by Shielding Abasic Sites in Single-Strand DNA.
Cell ( IF 45.5 ) Pub Date : 2018-12-13 , DOI: 10.1016/j.cell.2018.10.055 Kareem N Mohni 1 , Sarah R Wessel 1 , Runxiang Zhao 1 , Andrea C Wojciechowski 1 , Jessica W Luzwick 1 , Hillary Layden 1 , Brandt F Eichman 2 , Petria S Thompson 1 , Kavi P M Mehta 1 , David Cortez 1
Cell ( IF 45.5 ) Pub Date : 2018-12-13 , DOI: 10.1016/j.cell.2018.10.055 Kareem N Mohni 1 , Sarah R Wessel 1 , Runxiang Zhao 1 , Andrea C Wojciechowski 1 , Jessica W Luzwick 1 , Hillary Layden 1 , Brandt F Eichman 2 , Petria S Thompson 1 , Kavi P M Mehta 1 , David Cortez 1
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Abasic sites are one of the most common DNA lesions. All known abasic site repair mechanisms operate only when the damage is in double-stranded DNA. Here, we report the discovery of 5-hydroxymethylcytosine (5hmC) binding, ESC-specific (HMCES) as a sensor of abasic sites in single-stranded DNA. HMCES acts at replication forks, binds PCNA and single-stranded DNA, and generates a DNA-protein crosslink to shield abasic sites from error-prone processing. This unusual HMCES DNA-protein crosslink intermediate is resolved by proteasome-mediated degradation. Acting as a suicide enzyme, HMCES prevents translesion DNA synthesis and the action of endonucleases that would otherwise generate mutations and double-strand breaks. HMCES is evolutionarily conserved in all domains of life, and its biochemical properties are shared with its E. coli ortholog. Thus, HMCES is an ancient DNA lesion recognition protein that preserves genome integrity by promoting error-free repair of abasic sites in single-stranded DNA.
中文翻译：
HMCES 通过屏蔽单链 DNA 中的无碱基位点来保持基因组的完整性。
无碱基位点是最常见的 DNA 损伤之一。所有已知的无碱基位点修复机制仅在损伤位于双链 DNA 时才起作用。在这里，我们报告发现 5-羟甲基胞嘧啶 (5hmC) 结合，ESC 特异性 (HMCES) 作为单链 DNA 中无碱基位点的传感器。HMCES 作用于复制叉，结合 PCNA 和单链 DNA，并产生 DNA-蛋白质交联，以保护无碱基位点免受容易出错的处理。这种不寻常的 HMCES DNA-蛋白质交联中间体通过蛋白酶体介导的降解来解决。作为一种自杀酶，HMCES 可防止跨损伤 DNA 合成和内切核酸酶的作用，否则会产生突变和双链断裂。HMCES 在生命的所有领域都是进化保守的，其生化特性与其大肠杆菌直系同源物相同。因此，
更新日期：2018-12-14
中文翻译：
HMCES 通过屏蔽单链 DNA 中的无碱基位点来保持基因组的完整性。
无碱基位点是最常见的 DNA 损伤之一。所有已知的无碱基位点修复机制仅在损伤位于双链 DNA 时才起作用。在这里，我们报告发现 5-羟甲基胞嘧啶 (5hmC) 结合，ESC 特异性 (HMCES) 作为单链 DNA 中无碱基位点的传感器。HMCES 作用于复制叉，结合 PCNA 和单链 DNA，并产生 DNA-蛋白质交联，以保护无碱基位点免受容易出错的处理。这种不寻常的 HMCES DNA-蛋白质交联中间体通过蛋白酶体介导的降解来解决。作为一种自杀酶，HMCES 可防止跨损伤 DNA 合成和内切核酸酶的作用，否则会产生突变和双链断裂。HMCES 在生命的所有领域都是进化保守的，其生化特性与其大肠杆菌直系同源物相同。因此，
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