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Mutat Res Rev Mutat Res. 2016 Apr-Jun;768:53-67. doi: 10.1016/j.mrrev.2016.03.006. Epub 2016 Apr 7.

Mechanisms of mutagenesis: DNA replication in the presence of DNA damage.

Author information

1
Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China.
2
Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA.
3
Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, PR China. Electronic address: huidongzhang@tmmu.edu.cn.

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.

KEYWORDS:

DNA damage; DNA replication; Environmental mutagens; Mutation; Polymerase; Replisome

PMID:
27234563
PMCID:
PMC5237373
DOI:
10.1016/j.mrrev.2016.03.006
[Indexed for MEDLINE]
Free PMC Article

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