Mutagenesis resulting from depurination is an SOS process

Schaaper, Roel M.; Glickman, Barry W.; Loeb, Lawrence A.

doi:10.1016/0027-5107(82)90186-5

Cited by 72 publications

(36 citation statements)

References 14 publications

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“…Individual frames were indexed and scaled with the program XDS (58). The DMG-1 crystal belongs to space group P2 1 2 1 2, and the DMG-2 and DMG-3 crystals belong to space group P2 1 .…”

Section: X-ray Diffraction Data Collection and Processing-x-raymentioning

confidence: 99%

“…Cellular DNA is continuously attacked by physical agents and by various endogenous and exogenous chemicals to produce DNA damage products, including abasic sites (1,2), deamination products (3,4), oxidized adducts (e.g. 8-oxoG 3 (5-7)), alkyl lesions (particularly O 6 -alkyl G (8, 9)), UV-induced pyrimidine dimers, and 6-4 photoproducts (10,11), bis-electrophile-induced exocyclic DNA products (12)(13)(14)(15), and inter-and intra-strand DNA cross-links (9,15).…”

mentioning

confidence: 99%

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Structure-Function Relationships in Miscoding by Sulfolobus solfataricus DNA Polymerase Dpo4: GUANINE N2,N2-DIMETHYL SUBSTITUTION PRODUCES INACTIVE AND MISCODING POLYMERASE COMPLEXES

Zhang

Eoff

Kozekov

et al. 2009

Journal of Biological Chemistry

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“…Individual frames were indexed and scaled with the program XDS (58). The DMG-1 crystal belongs to space group P2 1 2 1 2, and the DMG-2 and DMG-3 crystals belong to space group P2 1 .…”

Section: X-ray Diffraction Data Collection and Processing-x-raymentioning

confidence: 99%

mentioning

confidence: 99%

Structure-Function Relationships in Miscoding by Sulfolobus solfataricus DNA Polymerase Dpo4: GUANINE N2,N2-DIMETHYL SUBSTITUTION PRODUCES INACTIVE AND MISCODING POLYMERASE COMPLEXES

Zhang

Eoff

Kozekov

et al. 2009

Journal of Biological Chemistry

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“…27). In E. coli, replication past AP sites requires SOS induction and umuC, recA, and recF (28,29). The DNA polymerase preferentially inserts dAMP and secondarily dTMP opposite the AP sites (27,30).…”

Section: Discussionmentioning

confidence: 99%

Spontaneous mutagenesis and oxidative damage to DNA in Salmonella typhimurium.

Storz

Christman

Sies

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

199

103

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Salmonella typhimurium strains containing deletions of oxyR, a positive regulator of defenses against oxidative stress, show 10-to 55-fold higher frequencies of spontaneous mutagenesis compared to otherwise isogenic oxyR+ control strains. The high spontaneous-mutation frequency in oxyR deletion strains is decreased by a factor of 3 when the strains are grown anaerobically. oxyR deletion strains show an increase in small deletion mutations and at least three of the six possible base-substitution mutations (TA to A-T, COG to T-A, and C-G to A-T). However, the largest increase in mutation frequency is observed for T-A to A-T transversions (40-to 146-fold), the base-substitution mutation most frequently caused by chemical oxidants. The introduction into oxyR deletion strains of multicopy plasmids carrying the oxyRregulated genes for catalase (kaIG) or alkyl hydroperoxide reductase (ahp) results in overexpression of the respective enzyme activities and decreases the number of spontaneous mutants to wild-type levels. The introduction into oxyR deletions of a plasmid carrying the gene for superoxide dismutase (sodA) decreases the mutation frequency by a factor of 5 in some strain backgrounds. Strains that contain a dominant oxyR mutation and overexpress proteins regulated by oxyR show lower spontaneous-mutation frequencies by a factor of 2. These results indicate that oxyR and oxyR-regulated genes play a significant role in defense against spontaneous oxidative DNA damage. The role of oxidative damage to DNA in "spontaneous" mutagenesis is discussed.Spontaneous mutations could arise by several different mechanisms. These include depurination, deamination, and other forms of DNA damage and repair, as well as recombination and errors in DNA replication (1). Among the potential sources of DNA damage, active oxygen species have become recognized as being of biological importance (2-7). Studies have shown that oxygen metabolism influences DNA damage in mammals (6, 7) and bacteria. Hartman et al. (8) showed that Salmonella typhimurium strains grown under aerobic conditions had increased frequencies of small deletion and frameshift mutations relative to strains grown anaerobically, while the frequency of G-C to AT transitions was depressed under the aerobic conditions. Recently, Farr et al. (9) showed that Escherichia coli mutants that lack both the manganese-and iron-containing superoxide dismutases (sodA sodB double mutants) have enhanced spontaneousmutation frequencies compared to wild-type strains during aerobic growth. In addition, several E. coli DNA repair mutants-recA xth double mutants (10), certain polA mutants (11), and polA recB double mutants (12)-form filaments and die aerobically, though they grow normally under anaerobic conditions.We recently have identified and characterized a gene, oxyR, that positively controls a regulon involved in cellular defenses against oxidative stress in both S. typhimurium and E. coli (13,14). A dominant mutant, oxyRi, is resistant to hydrogen peroxide and constitutively...

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“…These lesions are chemically very different from abasic sites, and they are repaired by different error-free repair mechanisms. However, they give rise to mutations by the same SOS mutagenesis pathway, and thus they are functional homologues, as far as induced mutagenesis is concerned (6,22,32). In particular, the 6 -4 photoadducts share with abasic sites the properties of being both blocking and miscoding (33).…”

Section: Formamido-pyrimidine Dna Glycosylase Inhibits Translesion Dnmentioning

confidence: 99%

Anti-mutagenic Activity of DNA Damage-binding Proteins Mediated by Direct Inhibition of Translesion Replication

Paz-Elizur

Barak

Livneh

1997

Journal of Biological Chemistry

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DNA lesions that block replication can be bypassed in Escherichia coli by a special DNA synthesis process termed translesion replication. This process is mutagenic due to the miscoding nature of the DNA lesions. We report that the repair enzyme formamido-pyrimidine DNA glycosylase and the general DNA damage recognition protein UvrA each inhibit specifically translesion replication through an abasic site analog by purified DNA polymerases I and II, and DNA polymerase III (␣ subunit) from E. coli. In vivo experiments suggest that a similar inhibitory mechanism prevents at least 70% of the mutations caused by ultraviolet light DNA lesions in E. coli. These results suggest that DNA damage-binding proteins regulate mutagenesis by a novel mechanism that involves direct inhibition of translesion replication. This mechanism provides anti-mutagenic defense against DNA lesions that have escaped DNA repair.Mutations caused by DNA-damaging agents play a key role in cancer via activation of oncogenes and inactivation of tumor suppressor genes (1). DNA repair is the major defense mechanism of cells against DNA damage and its deleterious effects. The major repair strategy in both prokaryotes and eukaryotes is excision repair. It involves excision of the damaged region from DNA, followed by re-synthesis using the complementary undamaged strand as a template (2). Two excision repair mechanisms are known for DNA damage: nucleotide excision repair (NER), 1 which operates on a wide variety of DNA lesions (3), and base excision repair (BER) which is more limited in its range of substrate specificity (4). The key step in these mechanisms is the recognition of DNA damage. In the bacterium Escherichia coli, the protein UvrA is responsible for the recognition of a broad range of DNA lesions that are repaired by NER, whereas in BER a series of DNA glycosylases with a much narrower range of specificity recognize and excise damaged or foreign bases from DNA (2).A DNA lesion that has escaped repair can cause a discontinuity in DNA in the form of a ssDNA region carrying the lesion. This occurs when the replication fork is blocked at the lesion (5, 6), or occasionally because of complications in nucleotide excision repair (7). This gap/lesion structure poses a problem for excision repair; an attempt to eliminate the lesion will cause a double-strand break, which is highly lethal, but on the other hand, the gap must be filled in for DNA replication to be completed and cell division to occur.Two tolerance mechanism that operate in E. coli are responsible for filling in the gap/lesion structures (2). A recombinational repair mechanism patches the gap via recombination using homologous sequences from the sister chromatid. This process does not remove the damaged base, but it enables an error-free bypass, resulting in the restoration of genome continuity. An alternative bypass mechanism, which is regulated by the SOS stress response, involves filling in of the gap by DNA synthesis. This translesion replication reaction is potentially mutagenic bec...

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Mutagenesis resulting from depurination is an SOS process

Cited by 72 publications

References 14 publications

Structure-Function Relationships in Miscoding by Sulfolobus solfataricus DNA Polymerase Dpo4: GUANINE N2,N2-DIMETHYL SUBSTITUTION PRODUCES INACTIVE AND MISCODING POLYMERASE COMPLEXES

Structure-Function Relationships in Miscoding by Sulfolobus solfataricus DNA Polymerase Dpo4: GUANINE N2,N2-DIMETHYL SUBSTITUTION PRODUCES INACTIVE AND MISCODING POLYMERASE COMPLEXES

Spontaneous mutagenesis and oxidative damage to DNA in Salmonella typhimurium.

Anti-mutagenic Activity of DNA Damage-binding Proteins Mediated by Direct Inhibition of Translesion Replication

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