Genomic approaches to DNA repair and mutagenesis.
Genomic approaches to DNA repair and mutagenesis.
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DOI：
10.1016/j.dnarep.2015.09.018
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发表时间：
2015-12
期刊：
影响因子：
3.8
通讯作者：
Roberts SA
中科院分区：
文献类型：
--
作者：
Wyrick JJ;Roberts SA
DNA 损伤对细胞来说是一个持续的威胁，会引起细胞毒性并诱导基因改变。细胞中DNA损伤的稳态丰度通过多种DNA修复机制最小化，包括DNA链断裂修复、错配修复、核苷酸切除修复、碱基切除修复和核糖核苷酸切除修复。这些途径消除染色体损伤的效率和机制主要是通过研究在大量基因组 DNA 中、附加型 DNA 构建体上或使用体外底物上确定的基因组位点处的损伤处理来表征的。然而，染色体的结构是异质的，由大量蛋白质结合的异染色质区域、开放调节区域、活跃转录的基因，甚至瞬时单链 DNA 区域组成。因此，DNA 修复途径在比使用以前的方法容易评估的更加多样化的染色体环境中发挥作用。最近开发 DNA 损伤、修复过程甚至突变的全基因组图谱的努力有望大大扩展我们对 DNA 修复和突变的理解。在这里，我们回顾了目前利用 DNA 损伤和突变的全基因组图谱来了解不同染色体环境如何影响 DNA 切除修复途径的努力。
DNA damage is a constant threat to cells, causing cytotoxicity as well as inducing genetic alterations. The steady-state abundance of DNA lesions in a cell is minimized by a variety of DNA repair mechanisms, including DNA strand break repair, mismatch repair, nucleotide excision repair, base excision repair, and ribonucleotide excision repair. The efficiencies and mechanisms by which these pathways remove damage from chromosomes have been primarily characterized by investigating the processing of lesions at defined genomic loci, among bulk genomic DNA, on episomal DNA constructs, or using in vitro substrates. However, the structure of a chromosome is heterogeneous, consisting of heavily protein-bound heterochromatic regions, open regulatory regions, actively transcribed genes, and even areas of transient single stranded DNA. Consequently, DNA repair pathways function in a much more diverse set of chromosomal contexts than can be readily assessed using previous methods. Recent efforts to develop whole genome maps of DNA damage, repair processes, and even mutations promise to greatly expand our understanding of DNA repair and mutagenesis. Here we review the current efforts to utilize whole genome maps of DNA damage and mutation to understand how different chromosomal contexts affect DNA excision repair pathways.