Abstract
Available DNA mutational spectra reveal that the number of mutants with multiple mutations ("multiples") is usually greater than expected from a random distribution of mutations among mutants. These overloads imply the occurrence of non-random clusters of mutations, probably generated during episodes of low-fidelity DNA synthesis. Excess multiples have been reported not only for viruses, bacteria, and eukaryotic cells but also for the DNA polymerases of phages T4 and RB69 in vitro. In the simplest case of a purified polymerase, non-random clusters may be generated by a subfraction of phenotypic variants able to introduce more errors per cycle of DNA synthesis than the normal enzyme. According to this hypothesis, excess multiples are not expected with non-processive polymerases even if they harbor rare mutator variants. DNA polymerase beta (Pol beta) is a mammalian DNA-repair polymerase with very low processivity. Although several Pol beta mutational spectra have been described, there is conflicting evidence on whether or not excess multiples occur, with spectra based on the HSV-tk system tending to show excess multiples. Excess multiples generated by Pol beta or any of its mutants might imply that the excesses of multiples obse...Continue Reading
References
Apr 5, 1975·Journal of Molecular Biology·L M Chang
Nov 1, 1991·Genetics·J Ninio
Feb 9, 1988·Biochemistry·J AbbottsS H Wilson
Dec 12, 1995·Biochemistry·K L MengeZ Hostomska
Jan 1, 1995·Methods in Enzymology·K Bebenek, T A Kunkel
Jun 4, 1996·Biochemistry·B G WerneburgM D Tsai
Feb 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·S L WashingtonJ B Sweasy
Apr 1, 1997·Nucleic Acids Research·K A EckertP L Vargo
Nov 5, 1997·The Journal of Biological Chemistry·A M ChagovetzB D Preston
Mar 28, 1998·Biochemistry·P L OpreskoK A Eckert
Jan 28, 1999·The Journal of Biological Chemistry·W P OsheroffT A Kunkel
Aug 16, 2001·The Journal of Biological Chemistry·M J LongleyW C Copeland
Nov 28, 2002·Genetics·Anna BebenekJohn W Drake
Aug 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·John W DrakeShyamal Peddada
Feb 9, 2006·Chemical Reviews·William A Beard, Samuel H Wilson
May 9, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jicheng WangSteve S Sommer
May 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·John W Drake
Aug 10, 2007·Critical Reviews in Biochemistry and Molecular Biology·John W Drake
Oct 6, 2007·Critical Reviews in Biochemistry and Molecular Biology·Rodrigo S GalhardoSusan M Rosenberg
Nov 28, 2007·PLoS Computational Biology·Martin WillensdorferMartin A Nowak
Feb 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jan StöhrDetlev Riesner
Oct 4, 2008·PLoS Genetics·Caleb GonzalezSusan M Rosenberg