Scicchitano David A
Department of Biology, 1009 Silver Center, 100 Washington Square East, New York University, New York, NY 10003, USA.
Mutat Res. 2005 Sep 4;577(1-2):146-54. doi: 10.1016/j.mrfmmm.2005.03.015.
The ability of a DNA lesion to block transcription is a function of many variables: (1) the ability of the RNA polymerase active site to accommodate the damaged base; (2) the size and shape of the adduct, which includes the specific modified base; (3) the stereochemistry of the adduct; (4) the base incorporated into the growing transcript; (5) and the local DNA sequence. Each of these parameters, either alone or in combination, can influence how a particular lesion in the genome will affect transcription elongation, resulting in potential clearance of the lesion via transcription-coupled DNA repair or in the formation of truncated or full-length transcripts that might encode defective proteins.
DNA损伤阻断转录的能力取决于许多变量:(1)RNA聚合酶活性位点容纳受损碱基的能力;(2)加合物的大小和形状,包括特定修饰碱基;(3)加合物的立体化学;(4)掺入正在生长的转录本中的碱基;(5)以及局部DNA序列。这些参数中的每一个,单独或组合起来,都可以影响基因组中特定损伤如何影响转录延伸,导致通过转录偶联DNA修复潜在地清除损伤,或形成可能编码缺陷蛋白的截短或全长转录本。