DNA protein crosslink proteolysis repair: From yeast to premature ageing and cancer in humans.
DNA protein crosslink proteolysis repair: From yeast to premature ageing and cancer in humans.
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DOI：
10.1016/j.dnarep.2018.08.025
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发表时间：
2018-11
期刊：
影响因子：
3.8
通讯作者：
Ramadan K
中科院分区：
文献类型：
--
作者：
Fielden J;Ruggiano A;Popović M;Ramadan K
DNA-蛋白质交联（DPC）是一种特殊类型的DNA损伤，由蛋白质共价和不可逆地结合到DNA上组成，其在暴露于物理和化学交联剂后产生。DPC可能体积庞大，从而对DNA复制和转录构成障碍。DPC在S期的持续存在导致DNA复制应激和基因组不稳定。DPC的毒性在癌症治疗中得到利用：许多常见的化疗药物通过诱导DPC形成来杀死癌细胞。最近几个实验室的工作发现了一种专门的DPC修复途径，即DPC蛋白水解（DPCP）修复。DPCP修复是由复制偶联的DNA依赖性金属蛋白酶进行的：酵母中的Wss 1和后生动物中的SPRTN。SPRTN的突变会导致人类和小鼠的过早衰老和肝癌;因此，有缺陷的DPC修复具有很大的临床影响。在本综述中，我们将修订目前的知识DPCP修复的机制和DPC蛋白酶活性的调节，同时突出了该领域最重要的悬而未决的问题。最后，我们将讨论错误的DPC修复对疾病和癌症治疗的影响。
DNA-protein crosslinks (DPCs) are a specific type of DNA lesion consisting of a protein covalently and irreversibly bound to DNA, which arise after exposure to physical and chemical crosslinking agents. DPCs can be bulky and thereby pose a barrier to DNA replication and transcription. The persistence of DPCs during S phase causes DNA replication stress and genome instability. The toxicity of DPCs is exploited in cancer therapy: many common chemotherapeutics kill cancer cells by inducing DPC formation. Recent work from several laboratories discovered a specialized repair pathway for DPCs, namely DPC proteolysis (DPCP) repair. DPCP repair is carried out by replication-coupled DNA-dependent metalloproteases: Wss1 in yeast and SPRTN in metazoans. Mutations in SPRTN cause premature ageing and liver cancer in humans and mice; thus, defective DPC repair has great clinical ramifications. In the present review, we will revise the current knowledge on the mechanisms of DPCP repair and on the regulation of DPC protease activity, while highlighting the most significant unresolved questions in the field. Finally, we will discuss the impact of faulty DPC repair on disease and cancer therapy.
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影响因子：
--
作者：
Ayala A;Muñoz MF;Argüelles S
通讯作者：
Argüelles S
影响因子：
64.5
作者：
Duxin JP;Dewar JM;Yardimci H;Walter JC
通讯作者：
Walter JC
影响因子：
16
作者：
Centore, Richard C.;Yazinski, Stephanie A.;Tse, Alice;Zou, Lee
通讯作者：
Zou, Lee
影响因子：
4.5
作者：
Heideker J;Prudden J;Perry JJ;Tainer JA;Boddy MN
通讯作者：
Boddy MN
DOI：
10.1083/jcb.201504005
发表时间：
2016-02-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Aparicio T;Baer R;Gottesman M;Gautier J
通讯作者：
Gautier J