Surviving the Sun: Repair and bypass of DNA UV lesions

Yang, Wei

doi:10.1002/pro.723

Cited by 52 publications

(67 citation statements)

References 69 publications

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“…3 B and C, and Table S4). UV irradiation induces the formation of pyrimidine dimers, whereas NIT introduces interstrand cross-links in DNA (27,28). Both forms of DNA damage can halt DNA replication if unrepaired.…”

Section: Activities Mediated By the Hrdc Domain Suppress Illegitimatementioning

confidence: 99%

Shuttling along DNA and directed processing of D-loops by RecQ helicase support quality control of homologous recombination

Harami

Seol

et al. 2017

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

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Cells must continuously repair inevitable DNA damage while avoiding the deleterious consequences of imprecise repair. Distinction between legitimate and illegitimate repair processes is thought to be achieved in part through differential recognition and processing of specific noncanonical DNA structures, although the mechanistic basis of discrimination remains poorly defined. Here, we show that Escherichia coli RecQ, a central DNA recombination and repair enzyme, exhibits differential processing of DNA substrates based on their geometry and structure. Through single-molecule and ensemble biophysical experiments, we elucidate how the conserved domain architecture of RecQ supports geometry-dependent shuttling and directed processing of recombination-intermediate [displacement loop (D-loop)] substrates. Our study shows that these activities together suppress illegitimate recombination in vivo, whereas unregulated duplex unwinding is detrimental for recombination precision. Based on these results, we propose a mechanism through which RecQ helicases achieve recombination precision and efficiency.RecQ | helicase | magnetic tweezers | single molecule | DNA unwinding

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Section: Activities Mediated By the Hrdc Domain Suppress Illegitimatementioning

confidence: 99%

Shuttling along DNA and directed processing of D-loops by RecQ helicase support quality control of homologous recombination

Harami

Seol

et al. 2017

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

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“…UvrA is one of the first gene products in which elevated expression can be detected upon DNA damage in the E. coli DNA damage response (19). This enzyme is part of the nucleotide excision repair (NER) pathway that detects DNA-distorting lesions, e.g., those produced by UV irradiation (34), and recruits the NER components to repair them. The E. coli DNA damage response also induces error-prone Y-family TLS DNA polymerases, Pol V and DinB, as well as B-family DNA Pol II, to perform DNA synthesis past replication-stalling lesions that have been left behind on the template DNA.…”

mentioning

confidence: 99%

Antibiotic Resistance Acquired through a DNA Damage-Inducible Response in Acinetobacter baumannii

Norton

Spilkia

Godoy

2013

Journal of Bacteriology

112

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Acinetobacter baumannii is an emerging nosocomial, opportunistic pathogen that survives desiccation and quickly acquires resistance to multiple antibiotics. Escherichia coli gains antibiotic resistances by expressing genes involved in a global response to DNA damage. Therefore, we asked whether A. baumannii does the same through a yet undetermined DNA damage response akin to the E. coli paradigm. We found that recA and all of the multiple error-prone DNA polymerase V (Pol V) genes, those organized as umuDC operons and unlinked, are induced upon DNA damage in a RecA-mediated fashion. Consequently, we found that the frequency of rifampin-resistant (Rif r ) mutants is dramatically increased upon UV treatment, alkylation damage, and desiccation, also in a RecA-mediated manner. However, in the recA insertion knockout strain, in which we could measure the recA transcript, we found that recA was induced by DNA damage, while uvrA and one of the unlinked umuC genes were somewhat derepressed in the absence of DNA damage. Thus, the mechanism regulating the A. baumannii DNA damage response is likely different from that in E. coli. Notably, it appears that the number of DNA Pol V genes may directly contribute to desiccation-induced mutagenesis. Sequences of the rpoB gene from desiccation-induced Rif r mutants showed a signature that was consistent with E. coli DNA polymerase V-generated base-pair substitutions and that matched that of sequenced A. baumannii clinical Rif r isolates. These data strongly support an A. baumannii DNA damage-inducible response that directly contributes to antibiotic resistance acquisition, particularly in hospitals where A. baumannii desiccates and tenaciously survives on equipment and surfaces.

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“…The Y-family DNA polymerases (pol , pol , pol , and REV1) are specialized in translesion synthesis (3,4). For example, pol is known for its unique role in correctly bypassing UV irradiation-induced cyclobutane pyrimidine dimer (5,6). Pol , on the other hand, is unable to copy past cyclobutane pyrimidine dimer but can proficiently insert T or C opposite adducted purines that are impaired in their capability of forming Watson-Crick base pairs (7)(8)(9).…”

mentioning

confidence: 99%

“…via reaction with trans-4-hydroperoxy-2-nonenal, a lipid peroxidation product (24)). In livers of unexposed rats or humans, the steady-state amounts of N 2 ,3-⑀G, 1,N 2 -⑀G, and 1,N 6 -⑀A have been estimated to be ϳ36, 30, and 12 lesions/cell, respectively (25).…”

mentioning

confidence: 99%

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases

Zhao

Pence

Christov

et al. 2012

Journal of Biological Chemistry

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N2,3-Ethenoguanine (N2,3-ϵG) is one of the exocyclic DNA adducts produced by endogenous processes (e.g. lipid peroxidation) and exposure to bioactivated vinyl monomers such as vinyl chloride, which is a known human carcinogen. Existing studies exploring the miscoding potential of this lesion are quite indirect because of the lability of the glycosidic bond. We utilized a 2′-fluoro isostere approach to stabilize this lesion and synthesized oligonucleotides containing 2′-fluoro-N2,3-ϵ-2′-deoxyarabinoguanosine to investigate the miscoding potential of N2,3-ϵG by Y-family human DNA polymerases (pols). In primer extension assays, pol η and pol κ replicated through N2,3-ϵG, whereas pol ι and REV1 yielded only 1-base incorporation. Steady-state kinetics revealed that dCTP incorporation is preferred opposite N2,3-ϵG with relative efficiencies in the order of pol κ > REV1 > pol η ≈ pol ι, and dTTP misincorporation is the major miscoding event by all four Y-family human DNA pols. Pol ι had the highest dTTP misincorporation frequency (0.71) followed by pol η (0.63). REV1 misincorporated dTTP and dGTP with much lower frequencies. Crystal structures of pol ι with N2,3-ϵG paired to dCTP and dTTP revealed Hoogsteen-like base pairing mechanisms. Two hydrogen bonds were observed in the N2,3-ϵG:dCTP base pair, whereas only one appears to be present in the case of the N2,3-ϵG:dTTP pair. Base pairing mechanisms derived from the crystal structures explain the slightly favored dCTP insertion for pol ι in steady-state kinetic analysis. Taken together, these results provide a basis for the mutagenic potential of N2,3-ϵG.

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Surviving the Sun: Repair and bypass of DNA UV lesions

Cited by 52 publications

References 69 publications

Shuttling along DNA and directed processing of D-loops by RecQ helicase support quality control of homologous recombination

Shuttling along DNA and directed processing of D-loops by RecQ helicase support quality control of homologous recombination

Antibiotic Resistance Acquired through a DNA Damage-Inducible Response in Acinetobacter baumannii

Basis of Miscoding of the DNA Adduct N2,3-Ethenoguanine by Human Y-family DNA Polymerases

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