Accuracy of Replication Past the T-C (6-4) Adduct

Horsfall, Michael; Lawrence, Christopher W.

doi:10.1006/jmbi.1994.1006

Cited by 97 publications

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“…Fujiwara and Iwai (42) show that the duplex containing G opposite the 3Ј-C of TC-(6 -4)PP is thermodynamically more stable than another duplex (42). Horsfall and Lawrence (20) studied the mutagenicity of TC-(6 -4)PP in E. coli cells and found that 66% of the bypass products have the correct TC sequence, 28% of the mutants having the TT sequence (20). Our observation that both G and A are incorporated opposite the 3Ј-C of TC-(6 -4)PP (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In TaqI assay, a 30-mer substrate was used, and a cleavage of the substrate produced a 14-base fragment. B, the 49-mer oligomer with no lesion (lanes 1-6), a TT-CPD (lanes 7-12), a TT-(6 -4)PP (lanes 13-16), or the 30-mer oligomer with TC-(6 -4)PP (lanes [17][18][19][20] were annealed to a 5Ј-32 Plabeled primer and then were mixed with Klenow fragment (2 units in lanes 1, 2, 7, 8, 13, 14, 17, and 18), dpol⌬C (500 fmol in lanes 3, 4, 9, 10, 15, and 16 or 1 nmol in lanes 19 and 20), or dpol⌬C (500 fmol in lanes 5, 6, 11, and 12). The reaction products were denatured by heating at 95°C for 5 min, and then excess amounts of the 49-mer oligonucleotide (lanes 1-16) or the 30-mer oligonucleotide (lanes 17-20), which does not contain a DNA lesion, were added and annealed to the newly synthesized DNA.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the TC-(6 -4)PP is less mutagenic than the TT-(6 -4)PP but more mutagenic than the TT-CPD. Of the mutations at this site, 80% were C to T transitions at the 3Ј base (20). Since TC to TT is frequently observed in DNA exposed to UV and (6 -4)PP forms most frequently in the TC sequence, the TC-(6 -4)PP could be a candidate for a strongly premutagenic lesion.…”

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confidence: 97%

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Mutagenic and Nonmutagenic Bypass of DNA Lesions byDrosophila DNA Polymerases dpolη and dpolι

Ishikawa

Uematsu

Mizukoshi

et al. 2001

Journal of Biological Chemistry

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cDNA sequences were identified and isolated that encode Drosophila homologues of human Rad30A and Rad30B called drad30A and drad30B. Here we show that the C-terminal-truncated forms of the drad30A and drad30B gene products, designated dpol⌬C and dpol⌬C, respectively, exhibit DNA polymerase activity. dpol⌬C and dpol⌬C efficiently bypass a cis-syn-cyclobutane thymine-thymine (TT) dimer in a mostly error-free manner. dpol⌬C shows limited ability to bypass a 6 -4-photoproduct ((6 -4)PP) at thymine-thymine (TT-(6 -4)PP) or at thymine-cytosine (TC-(6 -4)PP) in an error-prone manner. dpol⌬C scarcely bypasses these lesions. Thus, the fidelity of translesion synthesis depends on the identity of the lesion and on the polymerase. The human XPV gene product, hpol, bypasses cis-syn-cyclobutane thymine-thymine dimer efficiently in a mostly error-free manner but does not bypass TT-(6 -4)PP, whereas Escherichia coli DNA polymerase V (UmuD 2 C complex) bypasses both lesions, especially TT-(6 -4)PP, in an error-prone manner (Tang, M., Pham, P., Shen, X., Taylor, J. S., O'Donnell, M., Woodgate, R., and Goodman, M. F. (2000) Nature 404, 1014 -1018). Both dpol⌬C and DNA polymerase V preferentially incorporate GA opposite TT-(6 -4)PP. The chemical structure of the lesions and the similarity in the nucleotides incorporated suggest that structural information in the altered bases contribute to nucleotide selection during incorporation opposite these lesions by these polymerases.DNA is frequently damaged by environmental and endogenous genotoxic agents. Although various mechanisms exist to ensure that the majority of DNA damage is recognized and repaired and the integrity of the DNA is faithfully restored, some DNA lesions escape repair and persist in the cell. Unrepaired DNA lesions can block the progress of the replication machinery. To help resolve this problem, cells have specialized polymerases that carry out translesion DNA synthesis (TLS) 1 , which is a mechanism that permits nucleotides to be incorporated opposite lesions. After TLS bypasses the DNA damage, replication can continue with the normal replication machinery downstream of the site of the damage.Recently, a new family of DNA polymerases was identified called the UmuC/DinB/Rev1/Rad30 superfamily (1-3). Several of these polymerases participate in TLS (4 -11), and members of this protein family exhibit lower fidelity and processivity than replicative DNA polymerases (10, 12-15). The lower fidelity enables these polymerases to carry out TLS and the lower processivity facilitates dissociation of these enzymes after bypass of a lesion; this is important because it allows the normal replication machinery, with high fidelity and processivity, to preferentially carry out DNA synthesis distal to the lesion. However, TLS is mutagenic when the base inserted opposite the DNA lesion is different than the base normally inserted opposite an undamaged base at that site. The chemical structure of the lesion is an important determinant for mutagenic or nonmutagenic bypass during TLS. Irr...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

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Mutagenic and Nonmutagenic Bypass of DNA Lesions byDrosophila DNA Polymerases dpolη and dpolι

Ishikawa

Uematsu

Mizukoshi

et al. 2001

Journal of Biological Chemistry

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“…Studies on site specific mutagenesis in E. coli and yeast has helped to elucidate the intrinsic mutagenicity of the three bipyrimidine photoproducts (66)(67)(68)(69). In short, (6-4)PP and DewarPP are more mutagenic than the corresponding CPD.…”

Section: Biological Relevance Of Dewarppmentioning

confidence: 99%

Distribution and repair of bipyrimidine photoproducts in solar UV-irradiated mammalian cells. Possible role of Dewar photoproducts in solar mutagenesis

Perdiz

Gróf

Mezzina

et al. 2000

Journal of Biological Chemistry

146

177

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“…In addition, studies with a defined lesion in phage M13 DNA have shown that the extent and mutagenic consequences of translesion DNA synthesis vary and depend upon the specific type of DNA lesion encountered (3,4,25,(32)(33)(34).…”

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Isolation and characterization of novel plasmid-encoded umuC mutants

Woodgate¹,

Singh²,

Kulaeva³

et al. 1994

J Bacteriol

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Interestingly, these plasmid mutants fell into two classes: (i) 5 were expression mutants that produced either too little or too much wild-type UmuC protein, and (ii) 11 were plasmids with structural changes in the UmuC protein. Although hydroxylamine mutagenesis was random, most of the structural mutants identified in the screen were localized to two regions of the UmuC protein; four mutations were found in a stretch of 30 amino acids (residues 133 to 162) in the middle of the protein, while four other mutations (three of which resulted in a truncated UmuC protein) were localized in the last 50 carboxyl-terminal amino acid residues. These new plasmid umuC mutants, together with the previously identified chromosomal umuC25, umuC36, and umuC104 mutations that we have also cloned, should prove extremel useful in dissecting the genetic and biochemical activities of UmuC in mutagenic DNA repair.

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Accuracy of Replication Past the T-C (6-4) Adduct

Cited by 97 publications

References 0 publications

Mutagenic and Nonmutagenic Bypass of DNA Lesions byDrosophila DNA Polymerases dpolη and dpolι

Mutagenic and Nonmutagenic Bypass of DNA Lesions byDrosophila DNA Polymerases dpolη and dpolι

Distribution and repair of bipyrimidine photoproducts in solar UV-irradiated mammalian cells. Possible role of Dewar photoproducts in solar mutagenesis

Isolation and characterization of novel plasmid-encoded umuC mutants

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