All three SOS‐inducible DNA polymerases (Pol II, Pol IV and Pol V) are involved in induced mutagenesis

Most organisms contain several members of a recently discovered class of DNA polymerases (umuC/dinB superfamily) potentially involved in replication of damaged DNA. In Escherichia coli, only Pol V (umuDC) was known to be essential for base substitution mutagenesis induced by UV light or abasic sites. Here we show that, depending upon the nature of the DNA damage and its sequence context, the two additional SOS‐inducible DNA polymerases, Pol II (polB) and Pol IV (dinB), are also involved in error‐free and mutagenic translesion synthesis (TLS). For example, bypass of N‐2‐acetylaminofluorene (AAF) guanine adducts located within the NarI mutation hot spot requires Pol II for −2 frameshifts but Pol V for error‐free TLS. On the other hand, error‐free and −1 frameshift TLS at a benzo(a)pyrene adduct requires both Pol IV and Pol V. Therefore, in response to the vast diversity of existing DNA damage, the cell uses a pool of ‘translesional’ DNA polymerases in order to bypass the various DNA lesions.

[1]  J. Wagner,et al.  The beta clamp targets DNA polymerase IV to DNA and strongly increases its processivity. , 2000, EMBO reports.

[2]  R. Fuchs,et al.  The processing of a Benzo(a)pyrene adduct into a frameshift or a base substitution mutation requires a different set of genes in Escherichia coli , 2000, Molecular microbiology.

[3]  Roger Woodgate,et al.  Roles of E. coli DNA polymerases IV and V in lesion-targeted and untargeted SOS mutagenesis , 2000, Nature.

[4]  R. Fuchs,et al.  SOS mutagenesis results from up-regulation of translesion synthesis. , 1999, Journal of molecular biology.

[5]  Z. Livneh,et al.  The Mutagenesis Protein UmuC Is a DNA Polymerase Activated by UmuD′, RecA, and SSB and Is Specialized for Translesion Replication* , 1999, The Journal of Biological Chemistry.

[6]  T. Ogi,et al.  Mutation enhancement by DINB1, a mammalian homologue of the Escherichia coli mutagenesis protein DinB , 1999, Genes to cells : devoted to molecular & cellular mechanisms.

[7]  R. Fuchs,et al.  Replication of damaged DNA: molecular defect in xeroderma pigmentosum variant cells. , 1999, Mutation research.

[8]  E. Koonin,et al.  Human and mouse homologs of Escherichia coli DinB (DNA polymerase IV), members of the UmuC/DinB superfamily. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Epstein,et al.  Novel human and mouse homologs of Saccharomyces cerevisiae DNA polymerase eta. , 1999, Genomics.

[10]  E. G. Frank,et al.  UmuD'(2)C is an error-prone DNA polymerase, Escherichia coli pol V. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[11]  R. Woodgate,et al.  A phenotype for enigmatic DNA polymerase II: a pivotal role for pol II in replication restart in UV-irradiated Escherichia coli. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  J. Wagner,et al.  The dinB gene encodes a novel E. coli DNA polymerase, DNA pol IV, involved in mutagenesis. , 1999, Molecular cell.

[13]  Robert E. Johnson,et al.  hRAD30 mutations in the variant form of xeroderma pigmentosum. , 1999, Science.

[14]  Chikahide Masutani,et al.  The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase η , 1999, Nature.

[15]  F. Hanaoka,et al.  Xeroderma pigmentosum variant (XP‐V) correcting protein from HeLa cells has a thymine dimer bypass DNA polymerase activity , 1999, The EMBO journal.

[16]  M. Berardini,et al.  DNA Polymerase II (polB) Is Involved in a New DNA Repair Pathway for DNA Interstrand Cross-Links inEscherichia coli , 1999, Journal of bacteriology.

[17]  R. Fuchs,et al.  Sequence-dependent modulation of frameshift mutagenesis at NarI-derived mutation hot spots. , 1999, Journal of molecular biology.

[18]  Robert E. Johnson,et al.  Efficient bypass of a thymine-thymine dimer by yeast DNA polymerase, Poleta. , 1999, Science.

[19]  G. Walker,et al.  Mutagenesis and more: umuDC and the Escherichia coli SOS response. , 1998, Genetics.

[20]  M. Yamada,et al.  Multiple pathways for SOS-induced mutagenesis in Escherichia coli: an overexpression of dinB/dinP results in strongly enhancing mutagenesis in the absence of any exogenous treatment to damage DNA. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[21]  I. Lambert,et al.  SOS factors involved in translesion synthesis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[22]  M. Goodman,et al.  The Escherichia coli polB Locus Is Identical to dinA, the Structural Gene for DNA Polymerase II , 1997, The Journal of Biological Chemistry.

[23]  B. Edgar,et al.  Developmental Control of Cell Cycle Regulators: A Fly's Perspective , 1996, Science.

[24]  C. Lawrence,et al.  Deoxycytidyl transferase activity of yeast REV1 protein , 1996, Nature.

[25]  R. Fuchs,et al.  Cellular strategies for accommodating replication-hindering adducts in DNA: control by the SOS response in Escherichia coli. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[26]  C. Lawrence,et al.  Thymine-Thymine Dimer Bypass by Yeast DNA Polymerase ζ , 1996, Science.

[27]  R. Woodgate,et al.  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 , 1996, Journal of bacteriology.

[28]  R. Fuchs,et al.  Sequence determinants for -2 frameshift mutagenesis at NarI-derived hot spots. , 1995, Journal of molecular biology.

[29]  J. Trimarchi,et al.  Proofreading-defective DNA polymerase II increases adaptive mutation in Escherichia coli. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[30]  T. Kunkel,et al.  Purification and Properties of Wild-type and Exonuclease-deficient DNA Polymerase II from Escherichia coli(*) , 1995, The Journal of Biological Chemistry.

[31]  J. Lefèvre,et al.  NMR evidence of the stabilisation by the carcinogen N-2-acetylaminofluorene of a frameshift mutagenesis intermediate. , 1994, Nucleic acids research.

[32]  K. McEntee,et al.  Involvement of Escherichia coli DNA polymerase II in response to oxidative damage and adaptive mutation , 1994, Journal of bacteriology.

[33]  I. Tessman,et al.  DNA polymerase II of Escherichia coli in the bypass of abasic sites in vivo. , 1994, Genetics.

[34]  R. Fuchs,et al.  Greater susceptibility to mutations in lagging strand of DNA replication in Escherichia coli than in leading strand. , 1993, Science.

[35]  I. Lambert,et al.  DNA adduct-induced stabilization of slipped frameshift intermediates within repetitive sequences: implications for mutagenesis. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[36]  E. Loechler,et al.  Mutagenesis by the (+)-anti-diol epoxide of benzo[a]pyrene: what controls mutagenic specificity? , 1993, Biochemistry.

[37]  R. Woodgate.  Construction of a umuDC operon substitution mutation in Escherichia coli. , 1992, Mutation research.

[38]  R. Harvey,et al.  Polycyclic Aromatic Hydrocarbons: Chemistry and Carcinogenicity , 1992 .

[39]  I. Lambert,et al.  Carcinogen-induced frameshift mutagenesis in repetitive sequences. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[40]  J. E. Leclerc,et al.  The thymine-thymine pyrimidine-pyrimidone(6-4) ultraviolet light photoproduct is highly mutagenic and specifically induces 3' thymine-to-cytosine transitions in Escherichia coli. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[41]  P. Koehl,et al.  Single adduct mutagenesis: strong effect of the position of a single acetylaminofluorene adduct within a mutation hot spot. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[42]  M. Radman,et al.  Purification and characterization of an inducible Escherichia coli DNA polymerase capable of insertion and bypass at abasic lesions in DNA. , 1988, The Journal of biological chemistry.

[43]  G. Maenhaut-Michel,et al.  Role of RecA protein in untargeted UV mutagenesis of bacteriophage lambda: evidence for the requirement for the dinB gene. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[44]  M. Bichara,et al.  Carcinogen-induced mutation spectrum in wild-type, uvrA and umuC strains of Escherichia coli. Strain specificity and mutation-prone sequences. , 1984, Journal of molecular biology.

[45]  D. Grunberger,et al.  Molecular Biology of Mutagens and Carcinogens , 1983, Springer US.

[46]  R. Fuchs,et al.  Hot spots of frameshift mutations induced by the ultimate carcinogen N- acetoxy-N-2-acetylaminofluorene , 1981, Nature.

[47]  P. Hanawalt,et al.  Role of DNA polymerase II in repair replication in Escherichia coli. , 1973, Nature: New biology.

[48]  J A Miller,et al.  Carcinogenesis by chemicals: an overview--G. H. A. Clowes memorial lecture. , 1970, Cancer research.

[49]  J. Lefèvre,et al.  NMR data show that the carcinogen N-2-acetylaminofluorene stabilises an intermediate of -2 frameshift mutagenesis in a region of high mutation frequency. , 1996, European journal of biochemistry.

[50]  T. Sugimura,et al.  Potent Novel Mutagens Produced by Broiling Fish under Normal Conditions , 1980 .