Hang Bo
Department of Molecular Biology, Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, California 94720, USA.
Bioessays. 2004 Nov;26(11):1195-208. doi: 10.1002/bies.20130.
Exocyclic DNA adducts are mutagenic lesions that can be formed by both exogenous and endogenous mutagens/carcinogens. These adducts are structurally analogs but can differ in certain features such as ring size, conjugation, planarity and substitution. Although the information on the biological role of the repair activities for these adducts is largely unknown, considerable progress has been made on their reaction mechanisms, substrate specificities and kinetic properties that are affected by adduct structures. At least four different mechanisms appear to have evolved for the removal of specific exocyclic adducts. These include base excision repair, nucleotide excision repair, mismatch repair, and AP endonuclease-mediated repair. This overview highlights the recent progress in such areas with emphasis on structure-activity relationships. It is also apparent that more information is needed for a better understanding of the biological and structural implications of exocyclic adducts and their repair.
环外DNA加合物是可由外源性和内源性诱变剂/致癌物形成的致突变性损伤。这些加合物是结构类似物，但在某些特征上可能有所不同，如环大小、共轭、平面性和取代基。尽管关于这些加合物修复活性的生物学作用的信息在很大程度上尚不清楚，但在其受加合物结构影响的反应机制、底物特异性和动力学性质方面已经取得了相当大的进展。至少已经进化出四种不同的机制来去除特定的环外加合物。这些机制包括碱基切除修复、核苷酸切除修复、错配修复和AP核酸内切酶介导的修复。本综述强调了这些领域的最新进展，重点是构效关系。显然，为了更好地理解环外加合物及其修复的生物学和结构意义，还需要更多信息。
