尿嘧啶
鸟嘌呤
DNA糖基化酶
DNA
DNA修复
化学
尿嘧啶DNA糖基化酶
脱氨基
基底切除修复术
生物化学
DNA损伤
生物
基因
核苷酸
酶
作者
Nathaniel W. Holton,Erik D. Larson
出处
期刊:Mutagenesis
[Oxford University Press]
日期:2015-12-14
卷期号:31 (4): 385-392
被引量:4
标识
DOI:10.1093/mutage/gev083
摘要
Genome sequences that contain tandem repeats of guanine can form stable four-stranded structures known as G-quadruplex, or G4 DNA. While the molecular mechanisms are not fully defined, such guanine-rich loci are prone to mutagenesis and recombination. Various repair pathways function to reduce the potential for genome instability by correcting base damage and replication errors; however, it is not yet fully defined how well these processes function at G4 DNA. One frequent form of base damage occurs from cytidine deamination, resulting in deoxyuracil and UG mismatches. In duplex and single-stranded DNA, uracil bases are recognised and excised by uracil glycosylases. Here, we tested the efficiency of uracil glycosylase activity in vitro on uracil bases located directly adjacent to guanine repeats and G4 DNA. We show that uracil excision by bacterial UDG and human hUNG2 is reduced at uracils positioned directly 5′ or 3′ of a guanine tetrad. Control reactions using oligonucleotides disrupted for G4 formation or reaction conditions that do not favour G4 formation resulted in full uracil excision activity. Based on these in vitro results, we suggest that folding of guanine-rich DNA into G4 DNA results in a DNA conformation that is resistant to uracil glycosylase-initiated repair and this has the potential to increase the risk of instability at guanine repeats in the genome.
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