Binyan Liu1, Qizhen Xue1, Yong Tang1, Jia Cao1, F Peter Guengerich2, Huidong Zhang3. 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.
Environmental mutagens cause DNA damage that disturbs replication and produces mutations, leading to cancer anpan>d other diseases. We discuss mechanpan>isms of mutagenpan>esis resultinpan>g from DNA damage, from the level of DNA replication by a sinpan>gle polymerase to the complex DNA replisome of some typical model organpan>isms (inpan>cludinpan>g pan> class="Species">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: Hong Zang; Angela K Goodenough; Jeong-Yun Choi; Adriana Irimia; Lioudmila V Loukachevitch; Ivan D Kozekov; Karen C Angel; Carmelo J Rizzo; Martin Egli; F Peter Guengerich Journal: J Biol Chem Date: 2005-06-17 Impact factor: 5.157
Authors: Huidong Zhang; Seung-Joo Lee; Bin Zhu; Ngoc Q Tran; Stanley Tabor; Charles C Richardson Journal: Proc Natl Acad Sci U S A Date: 2011-05-23 Impact factor: 11.205
Authors: Huidong Zhang; Urban Bren; Ivan D Kozekov; Carmelo J Rizzo; Donald F Stec; F Peter Guengerich Journal: J Mol Biol Date: 2009-07-14 Impact factor: 5.469
Authors: Matthew T Cranford; Aurea M Chu; Joshua K Baguley; Robert J Bauer; Michael A Trakselis Journal: Nucleic Acids Res Date: 2017-08-21 Impact factor: 16.971