Our work is concerned with investigating DNA-damage induced mutagenesis, and the replication of damaged DNA which gives rise to these mutations, in budding yeast and E. coli. Such replication is used when unrepaired damage delays the progress of replication forks, and depends on a set of proteins at least partly different from those needed for replication on undamaged templates. Although only a minor cellular mechanism for coping with DNA damage, it is a major source of mutations. Understanding this process may therefore provide novel strategies for preventing cancer, since mutations commonly contribute to the development of this disease. To this end, we have cloned and sequenced yeast genes concerned with mutagenesis and, in collaboration with David Hinkle (Biology Department) examined the enzymatic properties of their purified products. In particular, we are investigating the properties of a new DNA polymerase, Pol zeta, a complex formed by the products of the REV3 and REV7 genes. The sole function of Pol zeta appears to be replication past damage sites in the DNA template, which it performs more efficiently than the major replicases. We are also investigating the properties of the REV1 gene product, which possesses a novel deoxycytidyl transferase activity that is required for replication past abasic lesions.

Studies with E. coli. carried out in collaboration with Roger Woodgate (NIH) and Myron Goodman (USC), are concerned with understanding the in vivo functions of the UmuD'C protein complex, which plays a crucial role in replication past DNA damage in this organism. In particular, we are attempting to identify the DNA polymerase holoenzyme subunits with which the complex interacts, and to determine the relative roles of DNA polymerase II and III. These questions are being investigated by transforming different mutant strains with single stranded vectors that carry a specified mutagenic lesion at a defined site. Such vectors are powerful tools for this purpose because they provide direct and independent estimates of the frequency of replication past the lesion and of the frequency with which mutations are induced by this process.

• Lawrence CW. Following the RAD6 pathway. DNA Repair (Amst). 2007 May 1; 6(5):676-86.
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• Zhang H, Gibbs PE, Lawrence CW. The Saccharomyces cerevisiae rev6-1 mutation, which inhibits both the lesion bypass and the recombination mode of DNA damage tolerance, is an allele of POL30, encoding proliferating cell nuclear antigen. Genetics. 2006 Aug; 173(4):1983-9.
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• Wang H, Hoffman PD, Lawrence C, Hays JB. Testing excision models for responses of mismatch-repair systems to UV photoproducts in DNA. Environ Mol Mutagen. 2006 May; 47(4):296-306.
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• Zhang H, Lawrence CW. The error-free component of the RAD6/RAD18 DNA damage tolerance pathway of budding yeast employs sister-strand recombination. Proc Natl Acad Sci U S A. 2005 Nov 1; 102(44):15954-9.
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• Hoffman PD, Wang H, Lawrence CW, Iwai S, Hanaoka F, Hays JB. Binding of MutS mismatch repair protein to DNA containing UV photoproducts, "mismatched" opposite Watson--Crick and novel nucleotides, in different DNA sequence contexts. DNA Repair (Amst). 2005 Aug 15; 4(9):983-93.
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• Diaz M, Lawrence C. An update on the role of translesion synthesis DNA polymerases in Ig hypermutation. Trends Immunol. 2005 Apr; 26(4):215-20.
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• Ozgenc AI, Szekeres ES, Lawrence CW. In vivo evidence for a recA-independent recombination process in Escherichia coli that permits completion of replication of DNA containing UV damage in both strands. J Bacteriol. 2005 Mar; 187(6):1974-84.
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• Gibbs PE, McDonald J, Woodgate R, Lawrence CW. The relative roles in vivo of Saccharomyces cerevisiae Pol eta, Pol zeta, Rev1 protein and Pol32 in the bypass and mutation induction of an abasic site, T-T (6-4) photoadduct and T-T cis-syn cyclobutane dimer. Genetics. 2005 Feb; 169(2):575-82.
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• Lawrence CW. Cellular functions of DNA polymerase zeta and Rev1 protein. Adv Protein Chem. 2004; 69:167-203.
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• Li Z, Zhang H, McManus TP, McCormick JJ, Lawrence CW, Maher VM. hREV3 is essential for error-prone translesion synthesis past UV or benzo[a]pyrene diol epoxide-induced DNA lesions in human fibroblasts. Mutat Res. 2002 Dec 29; 510(1-2):71-80.
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• Lawrence CW. Cellular roles of DNA polymerase zeta and Rev1 protein. DNA Repair (Amst). 2002 Jun 21; 1(6):425-35.
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• Borden A, O'Grady PI, Vandewiele D, Fernández de Henestrosa AR, Lawrence CW, Woodgate R. Escherichia coli DNA polymerase III can replicate efficiently past a T-T cis-syn cyclobutane dimer if DNA polymerase V and the 3' to 5' exonuclease proofreading function encoded by dnaQ are inactivated. J Bacteriol. 2002 May; 184(10):2674-81.
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• Lawrence CW. Classical mutagenesis techniques. Methods Enzymol. 2002; 350:189-99.
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• Burgers PM, Koonin EV, Bruford E, Blanco L, Burtis KC, Christman MF, Copeland WC, Friedberg EC, Hanaoka F, Hinkle DC, Lawrence CW, Nakanishi M, Ohmori H, Prakash L, Prakash S, Reynaud CA, Sugino A, Todo T, Wang Z, Weill JC, Woodgate R. Eukaryotic DNA polymerases: proposal for a revised nomenclature. J Biol Chem. 2001 Nov 23; 276(47):43487-90.
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• Ohmori H, Friedberg EC, Fuchs RP, Goodman MF, Hanaoka F, Hinkle D, Kunkel TA, Lawrence CW, Livneh Z, Nohmi T, Prakash L, Prakash S, Todo T, Walker GC, Wang Z, Woodgate R. The Y-family of DNA polymerases. Mol Cell. 2001 Jul; 8(1):7-8.
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• Lawrence CW, Maher VM. Eukaryotic mutagenesis and translesion replication dependent on DNA polymerase zeta and Rev1 protein. Biochem Soc Trans. 2001 May; 29(Pt 2):187-91.
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• Lawrence CW, Maher VM. Mutagenesis in eukaryotes dependent on DNA polymerase zeta and Rev1p. Philos Trans R Soc Lond B Biol Sci. 2001 Jan 29; 356(1405):41-6.
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• Nelson JR, Gibbs PE, Nowicka AM, Hinkle DC, Lawrence CW. Evidence for a second function for Saccharomyces cerevisiae Rev1p. Mol Microbiol. 2000 Aug; 37(3):549-54.
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• Gibbs PE, Wang XD, Li Z, McManus TP, McGregor WG, Lawrence CW, Maher VM. The function of the human homolog of Saccharomyces cerevisiae REV1 is required for mutagenesis induced by UV light. Proc Natl Acad Sci U S A. 2000 Apr 11; 97(8):4186-91.
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• O'Grady PI, Borden A, Vandewiele D, Ozgenc A, Woodgate R, Lawrence CW. Intrinsic polymerase activities of UmuD'(2)C and MucA'(2)B are responsible for their different mutagenic properties during bypass of a T-T cis-syn cyclobutane dimer. J Bacteriol. 2000 Apr; 182(8):2285-91.
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• Veaute X, Mari-Giglia G, Lawrence CW, Sarasin A. UV lesions located on the leading strand inhibit DNA replication but do not inhibit SV40 T-antigen helicase activity. Mutat Res. 2000 Feb 16; 459(1):19-28.
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• Lawrence CW, Gibbs PE, Murante RS, Wang XD, Li Z, McManus TP, McGregor WG, Nelson JR, Hinkle DC, Maher VM. Roles of DNA polymerase zeta and Rev1 protein in eukaryotic mutagenesis and translesion replication. Cold Spring Harb Symp Quant Biol. 2000; 65:61-9.
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• Wang H, Lawrence CW, Li GM, Hays JB. Specific binding of human MSH2.MSH6 mismatch-repair protein heterodimers to DNA incorporating thymine- or uracil-containing UV light photoproducts opposite mismatched bases. J Biol Chem. 1999 Jun 11; 274(24):16894-900.
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• Vandewiele D, Borden A, O'Grady PI, Woodgate R, Lawrence CW. Efficient translesion replication in the absence of Escherichia coli Umu proteins and 3'-5' exonuclease proofreading function. Proc Natl Acad Sci U S A. 1998 Dec 22; 95(26):15519-24.
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• Gibbs PE, McGregor WG, Maher VM, Nisson P, Lawrence CW. A human homolog of the Saccharomyces cerevisiae REV3 gene, which encodes the catalytic subunit of DNA polymerase zeta. Proc Natl Acad Sci U S A. 1998 Jun 9; 95(12):6876-80.
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• Horsfall MJ, Borden A, Lawrence CW. Mutagenic properties of the T-C cyclobutane dimer. J Bacteriol. 1997 May; 179(9):2835-9.
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• Nelson JR, Lawrence CW, Hinkle DC. Deoxycytidyl transferase activity of yeast REV1 protein. Nature. 1996 Aug 22; 382(6593):729-31.
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• Lawrence CW, Borden A, Woodgate R. Analysis of the mutagenic properties of the UmuDC, MucAB and RumAB proteins, using a site-specific abasic lesion. Mol Gen Genet. 1996 Jun 24; 251(4):493-8.
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• Nelson JR, Lawrence CW, Hinkle DC. Thymine-thymine dimer bypass by yeast DNA polymerase zeta. Science. 1996 Jun 14; 272(5268):1646-9.
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• Gentil A, Le Page F, Margot A, Lawrence CW, Borden A, Sarasin A. Mutagenicity of a unique thymine-thymine dimer or thymine-thymine pyrimidine pyrimidone (6-4) photoproduct in mammalian cells. Nucleic Acids Res. 1996 May 15; 24(10):1837-40.
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• Szekeres ES, Woodgate R, Lawrence CW. Substitution of mucAB or rumAB for umuDC alters the relative frequencies of the two classes of mutations induced by a site-specific T-T cyclobutane dimer and the efficiency of translesion DNA synthesis. J Bacteriol. 1996 May; 178(9):2559-63.
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• Carty MP, Lawrence CW, Dixon K. Complete replication of plasmid DNA containing a single UV-induced lesion in human cell extracts. J Biol Chem. 1996 Apr 19; 271(16):9637-47.
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• Lawrence CW, Hinkle DC. DNA polymerase zeta and the control of DNA damage induced mutagenesis in eukaryotes. Cancer Surv. 1996; 28:21-31.
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• Gibbs PE, Lawrence CW. Novel mutagenic properties of abasic sites in Saccharomyces cerevisiae. J Mol Biol. 1995 Aug 11; 251(2):229-36.
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• Gibbs PE, Borden A, Lawrence CW. The T-T pyrimidine (6-4) pyrimidinone UV photoproduct is much less mutagenic in yeast than in Escherichia coli. Nucleic Acids Res. 1995 Jun 11; 23(11):1919-22.
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• Torpey LE, Gibbs PE, Nelson J, Lawrence CW. Cloning and sequence of REV7, a gene whose function is required for DNA damage-induced mutagenesis in Saccharomyces cerevisiae. Yeast. 1994 Nov; 10(11):1503-9.
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• Horsfall MJ, Lawrence CW. Accuracy of replication past the T-C (6-4) adduct. J Mol Biol. 1994 Jan 14; 235(2):465-71.
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• Szymkowski DE, Lawrence CW, Wood RD. Repair by human cell extracts of single (6-4) and cyclobutane thymine-thymine photoproducts in DNA. Proc Natl Acad Sci U S A. 1993 Nov 1; 90(21):9823-7.
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• Gibbs PE, Lawrence CW. U-U and T-T cyclobutane dimers have different mutational properties. Nucleic Acids Res. 1993 Aug 25; 21(17):4059-65.
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• Lawrence CW, Gibbs PE, Borden A, Horsfall MJ, Kilbey BJ. Mutagenesis induced by single UV photoproducts in E. coli and yeast. Mutat Res. 1993 May; 299(3-4):157-63.
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• Gibbs PE, Kilbey BJ, Banerjee SK, Lawrence CW. The frequency and accuracy of replication past a thymine-thymine cyclobutane dimer are very different in Saccharomyces cerevisiae and Escherichia coli. J Bacteriol. 1993 May; 175(9):2607-12.
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• Singhal RK, Hinkle DC, Lawrence CW. The REV3 gene of Saccharomyces cerevisiae is transcriptionally regulated more like a repair gene than one encoding a DNA polymerase. Mol Gen Genet. 1992 Dec; 236(1):17-24.
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• LeClerc JE, Borden A, Lawrence CW. The thymine-thymine pyrimidine-pyrimidone(6-4) ultraviolet light photoproduct is highly mutagenic and specifically induces 3' thymine-to-cytosine transitions in Escherichia coli. Proc Natl Acad Sci U S A. 1991 Nov 1; 88(21):9685-9.
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• Lawrence CW. Classical mutagenesis techniques. Methods Enzymol. 1991; 194:273-81.
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• Lawrence CW, Banerjee SK, Borden A, LeClerc JE. T-T cyclobutane dimers are misinstructive, rather than non-instructive, mutagenic lesions. Mol Gen Genet. 1990 Jun; 222(1):166-8.
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• Lawrence CW, Borden A, Banerjee SK, LeClerc JE. Mutation frequency and spectrum resulting from a single abasic site in a single-stranded vector. Nucleic Acids Res. 1990 Apr 25; 18(8):2153-7.
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• Banerjee SK, Borden A, Christensen RB, LeClerc JE, Lawrence CW. SOS-dependent replication past a single trans-syn T-T cyclobutane dimer gives a different mutation spectrum and increased error rate compared with replication past this lesion in uninduced cells. J Bacteriol. 1990 Apr; 172(4):2105-12.
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• Morrison A, Christensen RB, Alley J, Beck AK, Bernstine EG, Lemontt JF, Lawrence CW. REV3, a Saccharomyces cerevisiae gene whose function is required for induced mutagenesis, is predicted to encode a nonessential DNA polymerase. J Bacteriol. 1989 Oct; 171(10):5659-67.
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• Banerjee SK, Christensen RB, Lawrence CW, LeClerc JE. Frequency and spectrum of mutations produced by a single cis-syn thymine-thymine cyclobutane dimer in a single-stranded vector. Proc Natl Acad Sci U S A. 1988 Nov; 85(21):8141-5.
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• Christensen JR, LeClerc JE, Tata PV, Christensen RB, Lawrence CW. UmuC function is not essential for the production of all targeted lacI mutations induced by ultraviolet light. J Mol Biol. 1988 Oct 5; 203(3):635-41.
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• LeClerc JE, Christensen JR, Tata PV, Christensen RB, Lawrence CW. Ultraviolet light induces different spectra of lacI sequence changes in vegetative and conjugating cells of Escherichia coli. J Mol Biol. 1988 Oct 5; 203(3):619-33.
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• Nisson PE, Lawrence CW. The isolation and characterization of ngm2, a mutation that affects nitrosoguanidine mutagenesis in yeast. Mol Gen Genet. 1986 Jul; 204(1):90-7.
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• Nisson PE, Lawrence CW. The isolation and characterization of an alkylating-agent-sensitive yeast mutant, ngs1. Mutat Res. 1986 May; 165(3):129-37.
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• Lawrence CW, Krauss BR, Christensen RB. New mutations affecting induced mutagenesis in yeast. Mutat Res. 1985 Jun-Jul; 150(1-2):211-6.
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• Lawrence CW, Christensen RB, Christensen JR. Identity of the photoproduct that causes lacI mutations in UV-irradiated Escherichia coli. J Bacteriol. 1985 Feb; 161(2):767-8.
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• Lawrence CW, Das G, Christensen RB. REV7, a new gene concerned with UV mutagenesis in yeast. Mol Gen Genet. 1985; 200(1):80-5.
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• Christensen RB, Christensen JR, Lawrence CW. Conjugation-dependent enhancement of induced and spontaneous mutation in the lacI gene of E. coli. Mol Gen Genet. 1985; 201(1):35-7.
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• Lawrence CW, Nisson PE, Christensen RB. UV and chemical mutagenesis in rev7 mutants of yeast. Mol Gen Genet. 1985; 200(1):86-91.
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• Christensen RB, Christensen JR, Koenig I, Lawrence CW. Untargeted mutagenesis induced by UV in the lacI gene of Escherichia coli. Mol Gen Genet. 1985; 201(1):30-4.
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• Lawrence CW, O'Brien T, Bond J. UV-induced reversion of his4 frameshift mutations in rad6, rev1, and rev3 mutants of yeast. Mol Gen Genet. 1984; 195(3):487-90.
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• Lawrence CW. Mutagenesis in Saccharomyces cerevisiae. Adv Genet. 1982; 21:173-254.
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• Lawrence CW, Christensen R, Schwartz A. Mechanisms of UV mutagenesis in yeast. Basic Life Sci. 1982; 20:109-20.
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• Lawrence CW, Christensen RB. The mechanism of untargeted mutagenesis in UV-irradiated yeast. Mol Gen Genet. 1982; 186(1):1-9.
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• Lawrence CW. Are pyrimidine dimers non-instructive lesions? Mol Gen Genet. 1981; 182(3):511-3.
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• McKee RH, Lawrence CW. Genetic analysis of gamma-ray mutagenesis in yeast. III. Double-mutant strains. Mutat Res. 1980 Mar; 70(1):37-48.
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• McKee RH, Lawrence CW. Genetic analysis of gamma-ray mutagenesis in yeast. I. Reversion in radiation-sensitive strains. Genetics. 1979 Oct; 93(2):361-73.
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• McKee RH, Lawrence CW. Genetic analysis of gamma-ray mutagenesis in yeast. II. Allele-specific control of mutagenesis. Genetics. 1979 Oct; 93(2):375-81.
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• Lawrence CW, Christensen RB. Metabolic suppressors of trimethoprim and ultraviolet light sensitivities of Saccharomyces cerevisiae rad6 mutants. J Bacteriol. 1979 Sep; 139(3):866-76.
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• Lawrence CW, Christensen RB. Ultraviolet-induced reversion of cyc1 alleles in radiation-sensitive strains of yeast. III. rev3 mutant strains. Genetics. 1979 Jun; 92(2):397-408.
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• Lawrence CW, Christensen RB. Absence of relationship between UV-induced reversion frequency and nucleotide sequence at the CYC1 locus of yeast. Mol Gen Genet. 1979; 177(1):31-8.
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• Lawrence CW, Christensen RB. Ultraviolet-induced reversion of cyc1 alleles in radiation sensitive strains of yeast. II. rev2 mutant strains. Genetics. 1978 Oct; 90(2):213-26.
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• Lawrence CW, Christensen RB. Ultraviolet-induced reversion of cyc1 alleles in radiation-sensitive strains of yeast. I. rev1 Mutant strains. J Mol Biol. 1978 Jun 15; 122(1):1-21.
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• Lawrence CW, Christensen R. UV mutagenesis in radiation-sensitive strains of yeast. Genetics. 1976 Feb; 82(2):207-32.
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• Lawrence CW, Sherman F, Jackson M, Gilmore RA. Mapping and gene conversion studies with the structural gene for iso-1-cytochrome C in yeast. Genetics. 1975 Dec; 81(4):615-29.
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• Lawrence CW, Stewart JW, Sherman F, Christensen R. Influence of repair on the specificity of ultraviolet-induced reversion of an ochre alleles of the structural gene for iso-1-cytochrome c. Basic Life Sci. 1975; 5A:397-8.
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• Lawrence CW, Stewart JW, Sherman F, Christensen R. Specificity and frequency of ultraviolet-induced reversion of an iso-1-cytochrome c ochre mutant in radiation-sensitive strains of yeast. J Mol Biol. 1974 May 5; 85(1):137-62.
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• Lawrence CW, Christensen R. Fine structure mapping in yeast with sunlamp radiation. Genetics. 1974 Apr; 76(4):723-33.
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• Lawrence CW. Dose dependence for radiation-induced allelic recombination in Chlamydomonas reinhardi. Mutat Res. 1970 Dec; 10(6):557-66.
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• Lawrence CW, Holt PD. Effect of gamma radiation and alpha particles on gene recombination in Chlamydomonas reinhardi. Mutat Res. 1970 Dec; 10(6):545-55.
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• Lawrence CW. The effects of dose duration in the influence of irradiation on recombination in Chlamydomonas. Mutat Res. 1965 Dec; 2(6):487-93.
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• Lawrence CW. The Orientation of Multiple Associations Resulting from Interchange Heterozygosity. Genetics. 1963 Mar; 48(3):347-50.
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