人类基因组突变景观的局部决定因素。

Local Determinants of the Mutational Landscape of the Human Genome.

机构信息

Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain; Research Program on Biomedical Informatics, Universitat Pompeu Fabra, Barcelona, Catalonia, Spain.

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.

出版信息

Cell. 2019 Mar 21;177(1):101-114. doi: 10.1016/j.cell.2019.02.051.

DOI:10.1016/j.cell.2019.02.051

PMID:30901533

Abstract

Large-scale chromatin features, such as replication time and accessibility influence the rate of somatic and germline mutations at the megabase scale. This article reviews how local chromatin structures -e.g., DNA wrapped around nucleosomes, transcription factors bound to DNA- affect the mutation rate at a local scale. It dissects how the interaction of some mutagenic agents and/or DNA repair systems with these local structures influence the generation of mutations. We discuss how this local mutation rate variability affects our understanding of the evolution of the genomic sequence, and the study of the evolution of organisms and tumors.

摘要

大规模染色质特征，如复制时间和可及性，会影响兆碱基尺度上的体细胞和种系突变率。本文综述了局部染色质结构（例如，缠绕在核小体周围的 DNA、结合到 DNA 上的转录因子）如何影响局部尺度上的突变率。本文剖析了一些诱变剂和/或 DNA 修复系统与这些局部结构的相互作用如何影响突变的产生。我们讨论了这种局部突变率的变化如何影响我们对基因组序列进化的理解，以及对生物体和肿瘤进化的研究。