title: Mechanisms of mutagenesis: DNA replication in the presence of DNA damage.
abstract: Environmental mutagens cause DNA damage that disturbs replication and produces mutations, leading to cancer and other diseases. We discuss mechanisms of mutagenesis resulting from DNA damage, from the level of DNA replication by a single polymerase to the complex DNA replisome of some typical model organisms (including bacteriophage T7, T4, Sulfolobus solfataricus, Escherichia coli, yeast and human). For a single DNA polymerase, DNA damage can affect replication in three major ways: reducing replication fidelity, causing frameshift mutations, and blocking replication. For the DNA replisome, protein interactions and the functions of accessory proteins can yield rather different results even with a single DNA polymerase. The mechanism of mutation during replication performed by the DNA replisome is a long-standing question. Using new methods and techniques, the replisomes of certain organisms and human cell extracts can now be investigated with regard to the bypass of DNA damage. In this review, we consider the molecular mechanism of mutagenesis resulting from DNA damage in replication at the levels of single DNA polymerases and complex DNA replisomes, including translesion DNA synthesis.
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China.
authors.forename: Binyan
authors.initials: B
authors.lastname: Liu
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China.
authors.forename: Qizhen
authors.initials: Q
authors.lastname: Xue
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
authors.forename: F Peter
authors.initials: FP
authors.lastname: Guengerich
authors.affiliation: Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China. Electronic address: huidongzhang@tmmu.edu.cn.
authors.forename: Huidong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018736:DNA Adducts; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair; D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects; D020022:Genetic Predisposition to Disease; D006801:Humans; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D011485:Protein Binding
chemical_list: D018736:DNA Adducts; D009153:Mutagens; D004259:DNA-Directed DNA Polymerase
keywords: DNA damage; DNA replication; Environmental mutagens; Mutation; Polymerase; Replisome