DNA-protein crosslinks: their induction, repair, and biological consequences

被引:252
作者
Barker, S [1 ]
Weinfeld, M [1 ]
Murray, D [1 ]
机构
[1] Univ Alberta, Cross Canc Inst, Div Expt Oncol, Dept Oncol, Edmonton, AB T6G 1Z2, Canada
基金
加拿大健康研究院;
关键词
DNA-protein crosslink; DNA repair; DNA damage;
D O I
10.1016/j.mrrev.2004.11.003
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The covalent crosslinking of proteins to DNA presents a major physical challenge to the DNA metabolic machinery. DNA-protein crosslinks (DPCs) are induced by a variety of endogenous and exogenous agents (including, paradoxically, agents that are known to cause cancer as well as agents that are used to treat cancer), and yet they have not received as much attention as other types of DNA damage. This review summarizes the current state of knowledge of DPCs in terms of their induction, structures, biological consequences and possible mechanisms of repair. DPCs can be formed through several different chemistries, which is likely to affect the stability and repair of these lesions, as well as their biological consequences. The considerable discrepancy in the DPC literature reflects both the varying chemistries of this heterogeneous group of lesions and the fact that a number of different methods have been used for their analysis. In particular, research in this area has long been hampered by the inability to chemically define these lesions in intact cells and tissues. However, the emergence of proteomics as a tool for identifying specific proteins that become crosslinked to DNA has heralded a new era in our ability to study these lesions. Although there are still many unanswered questions, the identification of specific proteins crosslinked to DNA should facilitate our understanding of the down-stream effects of these lesions. (c) 2004 Elsevier B.V. All rights reserved.
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页码:111 / 135
页数:25
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