Breaking bad: The mutagenic effect of DNA repair

doi:10.1016/j.dnarep.2015.04.012

	Breaking bad: The mutagenic effect of DNA repair
	Chen, Jia1 ; Furano, Anthony V.2
	2015-08
发表期刊	DNA REPAIR
ISSN	1568-7864
卷号	32 页码:43-51
发表状态	已发表
DOI	10.1016/j.dnarep.2015.04.012
摘要	Species survival depends on the faithful replication of genetic information, which is continually monitored and maintained by DNA repair pathways that correct replication errors and the thousands of lesions that arise daily from the inherent chemical lability of DNA and the effects of genotoxic agents. Nonetheless, neutrally evolving DNA (not under purifying selection) accumulates base substitutions with time (the neutral mutation rate). Thus, repair processes are not 100% efficient. The neutral mutation rate varies both between and within chromosomes. For example it is 10-50 fold higher at CpGs than at non-CpG positions. Interestingly, the neutral mutation rate at non-CpG sites is positively correlated with CpG content. Although the basis of this correlation was not immediately apparent, some bioinformatic results were consistent with the induction of non-CpG mutations by DNA repair at flanking CpG sites. Recent studies with a model system showed that in vivo repair of preformed lesions (mismatches, abasic sites, single stranded nicks) can in fact induce mutations in flanking DNA. Mismatch repair (MMR) is an essential component for repair-induced mutations, which can occur as distant as 5 kb from the introduced lesions. Most, but not all, mutations involved the C of TpCpN (G of NpGpA) which is the target sequence of the C-preferring single-stranded DNA specific APOBEC deaminases. APOBEC-mediated mutations are not limited to our model system: Recent studies by others showed that some tumors harbor mutations with the same signature, as can intermediates in RNA-guided endonuclease-mediated genome editing. APOBEC deaminases participate in normal physiological functions such as generating mutations that inactivate viruses or endogenous retrotransposons, or that enhance immunoglobulin diversity in B cells. The recruitment of normally physiological error-prone processes during DNA repair would have important implications for disease, aging and evolution. This perspective briefly reviews both the bioinformatic and biochemical literature relevant to repair-induced mutagenesis and discusses future directions required to understand the mechanistic basis of this process. Published by Elsevier B.V.
关键词	DNA repair Mutagenesis APOBEC deaminase Base excision repair Mismatch repair Cancer CRISPR/Cas
收录类别	SCI
语种	英语
WOS研究方向	Genetics & Heredity ; Toxicology
WOS类目	Genetics & Heredity ; Toxicology
WOS记录号	WOS:000359169500007
出版者	ELSEVIER SCIENCE BV
WOS关键词	BASE EXCISION-REPAIR ; SHUTTLE VECTOR PLASMID ; MALE-DRIVEN EVOLUTION ; MISMATCH REPAIR ; MAMMALIAN-CELLS ; HUMAN CANCERS ; SOMATIC HYPERMUTATION ; MUTATION-RATE ; HUMAN GENOME ; ERROR-PRONE
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2167
专题	生命科学与技术学院_PI研究组_陈佳组
通讯作者	Furano, Anthony V.
作者单位	1.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China 2.NIDDK, Sect Genom Struct & Funct, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA
第一作者单位	生命科学与技术学院
第一作者的第一单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Chen, Jia,Furano, Anthony V.. Breaking bad: The mutagenic effect of DNA repair[J]. DNA REPAIR,2015,32:43-51.
APA	Chen, Jia,&Furano, Anthony V..(2015).Breaking bad: The mutagenic effect of DNA repair.DNA REPAIR,32,43-51.
MLA	Chen, Jia,et al."Breaking bad: The mutagenic effect of DNA repair".DNA REPAIR 32(2015):43-51.