Mass Spectrometry-Based Tools to Characterize DNA-Protein Cross-Linking by Bis-Electrophiles.
Mass Spectrometry-Based Tools to Characterize DNA-Protein Cross-Linking by Bis-Electrophiles.
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DOI：
10.1111/bcpt.12751
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发表时间：
2017-09
影响因子：
3.1
通讯作者：
Tretyakova NY
中科院分区：
文献类型：
--
作者：
Groehler A 4th;Degner A;Tretyakova NY
DNA-蛋白质交联（DPC）是由于暴露于内源性和外源性试剂（包括活性氧物质、紫外线、电离辐射、环境试剂（例如过渡金属、甲醛、1，2-二溴乙烷、1，3-丁二烯）和常见化疗剂）而在细胞中形成的异常庞大的DNA加合物。共价DPC具有细胞毒性和致突变性，因为它们能够干扰忠实的DNA复制并阻止准确的基因表达。我们理解DPC形成的生物学意义的关键是确定最容易形成这些异常庞大和复杂病变的蛋白质，并量化细胞和组织中DNA-蛋白质交联的程度。基于自下而上质谱的蛋白质组学的最新进展允许在体外和体内暴露于交联剂后对整个蛋白DPC内收体进行无偏倚的评估。本文综述了当前和新兴的DPC分离和分析方法，基于质谱的蛋白质组学。我们强调这些新的方法，如甲醛，1，2，3，4-diepoxybutane，氮muclide，顺铂诱导的DPC病变的研究的成功应用的几个例子。
DNA-protein cross-links (DPCs) are unusually bulky DNA adducts that form in cells as a result of exposure to endogenous and exogenous agents including reactive oxygen species, ultraviolet light, ionizing radiation, environmental agents (e.g. transition metals, formaldehyde, 1,2-dibromoethane, 1,3-butadiene), and common chemotherapeutic agents. Covalent DPCs are cytotoxic and mutagenic due to their ability to interfere with faithful DNA replication and prevent accurate gene expression. Key to our understanding of the biological significance of DPC formation is identifying the proteins most susceptible to forming these unusually bulky and complex lesions and quantifying the extent of DNA-protein cross-linking in cells and tissues. Recent advances in bottom-up mass spectrometry-based proteomics have allowed for an unbiased assessment of the whole protein DPC adductome following in vitro and in vivo exposures to cross-linking agents. This review summarizes current and emerging methods for DPC isolation and analysis by mass spectrometry-based proteomics. We highlight several examples of successful applications of these novel methodologies to studies of DPC lesions induced by bis-electrophiles such as formaldehyde, 1,2,3,4-diepoxybutane, nitrogen mustards, and cisplatin.
影响因子：
2.4
作者：
Takano H;Yanagisawa R;Inoue K
通讯作者：
Inoue K