Alternative repair pathways for UV-induced DNA damage

Yasui, Akira; McCready, Shirley

doi:10.1002/(sici)1521-1878(199804)20:4<291::aid-bies5>3.0.co;2-t

Cited by 67 publications

(41 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are photolyases specific for either CPDs or (6-4)PPs (reviewed in Refs. [47][48][49][50]. To repair CPDs, the CPD photolyase gene of P. tridactylis (34) was introduced, and for repairing (6-4)PPs, the (6-4) photolyase gene from A. thaliana (36) was introduced into the mouse embryonic fibroblast cell line.…”

Section: Resultsmentioning

confidence: 99%

Cyclobutane Pyrimidine Dimers Are Responsible for the Vast Majority of Mutations Induced by UVB Irradiation in Mammalian Cells

You

Lee

Yoon

et al. 2001

Journal of Biological Chemistry

Self Cite

263

178

View full text Add to dashboard Cite

The most prevalent DNA lesions induced by UVB are the cyclobutane pyrimidine dimers (CPDs) and the pyrimidine (6-4) pyrimidone photoproducts ((6-4)PPs). It has been a long standing controversy as to which of these photoproduct is responsible for mutations in mammalian cells. Here we have introduced photoproduct-specific DNA photolyases into a mouse cell line carrying the transgenic mutation reporter genes lacI and cII. Exposure of the photolyase-expressing cell lines to photoreactivating light resulted in almost complete repair of either CPDs or (6-4)PPs within less than 3 h. The mutations produced by the remaining, nonrepaired photoproducts were scored. The mutant frequency in the cII gene after photoreactivation by CPD photolyase was reduced from 127 ؋ 10 ؊5 to 34 ؋ 10 ؊5 (background, 8 -10 ؋ 10 ؊5 ). Photoreactivation with (6-4) photolyase did not lower the mutant frequency appreciably. In the lacI gene the mutant frequency after photoreactivation repair of CPDs was reduced from 148 ؋ 10 ؊5 to 28 ؋ 10 ؊5(background, 6 -10 ؋ 10 ؊5 ). Mutation spectra obtained with and without photoreactivation by CPD photolyase indicated that the remaining mutations were derived from background mutations, unrepaired CPDs, and other DNA photopoducts including perhaps a small contribution from (6-4)PPs. We conclude that CPDs are responsible for at least 80% of the UVB-induced mutations in this mammalian cell model.The UV component of sunlight is responsible for the induction of skin tumors, most notably basal cell and squamous cell carcinomas and probably also melanomas (1, 2). Mutations in the p53 gene have been found in a large percentage of human skin malignancies (3-6). The most frequent p53 mutations in skin tumors are C to T or CC to TT mutations involving dipyrimidine sequences. These are considered characteristic mutational changes that can be ascribed to solar UV irradiation (7).The most abundant UV-induced DNA photoproducts are the cis-syn cyclobutane pyrimidine dimers (CPDs) 1 and the pyrimidine (6-4) pyrimidone photoproducts ((6-4)PPs). Both lesions are produced by UVB (280 -320 nm) and UVC (200 -280 nm) irradiation in DNA (8, 9). Most of the mutagenic and carcinogenic action of sunlight has been ascribed to the UVB portion of the solar spectrum (10) with a possible role for UVA (320 -400 nm) in the induction of melanoma (11). The absorption of UVA photons by DNA is rather weak, and it is thought that indirect damaging mechanisms may involve endogenous chromophores as radiation absorbing intermediates (12). These can generate reactive oxygen species, which may then damage DNA. Of all lesions formed in DNA after UVB irradiation, the CPD is considered one of the most important ones based on its relatively high abundance, slow repair, and known mutagenicity (8, 9, 13). However, a strong case can be made that the (6-4)PPs are equally if not more important than the CPDs for inducing mutations. C to T transitions can be induced by both CPDs and (6-4)PPs in mutagenesis studies using site-specific photolesions, and (6-4)PP...

show abstract

Section: Resultsmentioning

confidence: 99%

Cyclobutane Pyrimidine Dimers Are Responsible for the Vast Majority of Mutations Induced by UVB Irradiation in Mammalian Cells

You

Lee

Yoon

et al. 2001

Journal of Biological Chemistry

Self Cite

263

178

View full text Add to dashboard Cite

show abstract

“…FEN1 is another structure-specific DNA endonuclease, and its substrates include "flaps" of DNA that result from DNA polymerase-mediated displacement of single-stranded DNA 3Ј to the newly synthesized DNA. Such structures are thought to occur during lagging-strand DNA synthesis and possibly during BER and UVDE-mediated excision repair (30,51). In support of a role for S. pombe Rad2 in DNA repair, rad2 strains have a reduced ability to repair cyclobutane pyrimidine dimers and 6-4 photoproducts and presumably accounts for the UV-sensitive phenotype (35).…”

Section: Resultsmentioning

confidence: 99%

Contribution of Base Excision Repair, Nucleotide Excision Repair, and DNA Recombination to Alkylation Resistance of the Fission Yeast Schizosaccharomyces pombe

Memişoğlu

Samson

2000

J Bacteriol

View full text Add to dashboard Cite

DNA damage is unavoidable, and organisms across the evolutionary spectrum possess DNA repair pathways that are critical for cell viability and genomic stability. To understand the role of base excision repair (BER) in protecting eukaryotic cells against alkylating agents, we generated Schizosaccharomyces pombe strains mutant for the mag1 3-methyladenine DNA glycosylase gene. We report that S. pombe mag1 mutants have only a slightly increased sensitivity to methylation damage, suggesting that Mag1-initiated BER plays a surprisingly minor role in alkylation resistance in this organism. We go on to show that other DNA repair pathways play a larger role than BER in alkylation resistance. Mutations in genes involved in nucleotide excision repair (rad13) and recombinational repair (rhp51) are much more alkylation sensitive than mag1 mutants. In addition, S. pombe mutant for the flap endonuclease rad2 gene, whose precise function in DNA repair is unclear, were also more alkylation sensitive than mag1 mutants. Further, mag1 and rad13 interact synergistically for alkylation resistance, and mag1 and rhp51 display a surprisingly complex genetic interaction. A model for the role of BER in the generation of alkylation-induced DNA strand breaks in S. pombe is discussed.DNA damage emanates from the inherent chemical instability of nucleic acids, from errors made by DNA polymerase during DNA replication, and from exposure to DNA-damaging agents present in the environment or produced by certain endogenous cellular processes (reviewed in reference 15). All organisms possess a panel of DNA repair mechanisms to repair damaged DNA. DNA excision repair pathways recognize and remove damaged segments from one DNA strand and then resynthesize new DNA, using the opposing undamaged strand as a template. Excision repair includes base excision repair (BER) and nucleotide excision repair (NER). An alternative approach to handling damaged DNA is by recombinational repair. These DNA repair pathways have been best characterized in Escherichia coli, but analogous pathways have been found in all organisms examined to date (15).BER initiation occurs by the action of DNA glycosylases that recognize specific types of damaged or abnormal DNA bases and cleave the glycosylic bond linking the base to the sugarphosphate backbone. DNA glycosylases recognize bases such as uracil, deaminated adenine (hypoxanthine), and certain alkylated and oxidized purines and pyrimidines (reviewed in references 10, 15, 21, 31, and 47). Releasing a damaged base from the DNA produces an apurinic/apyrimidinic (AP) site, and it is worth noting that AP sites are themselves a form of DNA damage. In addition to being generated by DNA glycosylases, AP sites can be formed spontaneously. AP endonucleases (which cleave 5Ј to the AP site) or AP lyases (which cleave 3Ј to the AP site) cleave the DNA backbone adjacent to the AP site. AP endonuclease produces a 5Ј-deoxyribose phosphate moiety, which must be removed to allow subsequent DNA ligation; removal occurs by the action of deoxyr...

show abstract

“…In S. pombe it is known that the Uve1 enzyme nicks DNA immediately 5Ј of the DNA lesion (30). Following this, the nick is processed by one of two separate pathways, which involve the FEN1 homologue Rad2 and the recombination machinery (53). In addition to the physical removal of UV-induced DNA damage, mechanisms exist to bypass the lesions by translesion synthesis or recombination.…”

Section: Rqh1 Acts With Recombination Proteinsmentioning

confidence: 99%

Role for the Fission Yeast RecQ Helicase in DNA Repair in G₂

Laursen

Ampatzidou

Andersen

et al. 2003

Molecular and Cellular Biology

View full text Add to dashboard Cite

Members of the RecQ helicase subfamily are mutated in several human genomic instability syndromes, such as Bloom, Werner, and Rothmund-Thomson syndromes. We show that Rqh1, the single Schizosaccharomyces pombe homologue, is a 3-to-5 helicase and exists with Top3 in a high-molecular-weight complex. top3 deletion is inviable, and this is suppressed by concomitant loss of rqh1 helicase activity or loss of recombination functions. This is consistent with RecQ helicases in other systems. By using epistasis analysis of the UV radiation sensitivity and by analyzing the kinetics of Rhp51 (Rad51 homologue), Rqh1, and Top3 focus formation in response to UV in synchronized cells, we identify the first evidence of a function for Rqh1 and Top3 in the repair of UV-induced DNA damage in G 2 . Our data provide evidence that Rqh1 functions after Rad51 focus formation during DNA repair. We also identify a function for Rqh1 upstream of recombination in an Rhp18-dependent (Rad18 homologue) pathway. The model that these data allow us to propose helps to reconcile different interpretations of RecQ family helicase function that have arisen between work based on the S. pombe system and models based on studies of Saccharomyces cerevisiae SGS1 suggesting that RecQ helicases act before Rad51.

show abstract

Alternative repair pathways for UV-induced DNA damage

Cited by 67 publications

References 34 publications

Cyclobutane Pyrimidine Dimers Are Responsible for the Vast Majority of Mutations Induced by UVB Irradiation in Mammalian Cells

Cyclobutane Pyrimidine Dimers Are Responsible for the Vast Majority of Mutations Induced by UVB Irradiation in Mammalian Cells

Contribution of Base Excision Repair, Nucleotide Excision Repair, and DNA Recombination to Alkylation Resistance of the Fission Yeast Schizosaccharomyces pombe

Role for the Fission Yeast RecQ Helicase in DNA Repair in G₂

Contact Info

Product

Resources

About

Alternative repair pathways for UV-induced DNA damage

Cited by 67 publications

References 34 publications

Cyclobutane Pyrimidine Dimers Are Responsible for the Vast Majority of Mutations Induced by UVB Irradiation in Mammalian Cells

Cyclobutane Pyrimidine Dimers Are Responsible for the Vast Majority of Mutations Induced by UVB Irradiation in Mammalian Cells

Contribution of Base Excision Repair, Nucleotide Excision Repair, and DNA Recombination to Alkylation Resistance of the Fission Yeast Schizosaccharomyces pombe

Role for the Fission Yeast RecQ Helicase in DNA Repair in G2

Contact Info

Product

Resources

About

Role for the Fission Yeast RecQ Helicase in DNA Repair in G₂