Mol C D, Parikh S S, Putnam C D, Lo T P, Tainer J A
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037, USA.
Annu Rev Biophys Biomol Struct. 1999;28:101-28. doi: 10.1146/annurev.biophys.28.1.101.
Recent structural and biochemical studies have begun to illuminate how cells solve the problems of recognizing and removing damaged DNA bases. Bases damaged by environmental, chemical, or enzymatic mechanisms must be efficiently found within a large excess of undamaged DNA. Structural studies suggest that a rapid damage-scanning mechanism probes for both conformational deviations and local deformability of the DNA base stack. At susceptible lesions, enzyme-induced conformational changes lead to direct interactions with specific damaged bases. The diverse array of damaged DNA bases are processed through a two-stage pathway in which damage-specific enzymes recognize and remove the base lesion, creating a common abasic site intermediate that is processed by damage-general repair enzymes to restore the correct DNA sequence.
最近的结构和生化研究已开始阐明细胞如何解决识别和去除受损DNA碱基的问题。通过环境、化学或酶促机制受损的碱基必须在大量未受损的DNA中被有效找到。结构研究表明，一种快速的损伤扫描机制会探测DNA碱基堆积的构象偏差和局部可变形性。在易损位点，酶诱导的构象变化会导致与特定受损碱基的直接相互作用。各种各样的受损DNA碱基通过一个两阶段途径进行处理，其中损伤特异性酶识别并去除碱基损伤，产生一个共同的无碱基位点中间体，该中间体由损伤通用修复酶进行处理以恢复正确的DNA序列。
