DNA excision-repair processes in human cells can eliminate the cytotoxic and mutagenic consequences of ultraviolet irradiation

Maher, Veronica M.; Dorney, Delia J.; Mendrala, Alan L.; Konze‐Thomas, Beate; McCormick, J. Justin

doi:10.1016/0027-5107(79)90087-3

Cited by 236 publications

(95 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2B). These results are consistent with previous reports of UV-induced mutagenesis in reporter genes (11,(13)(14)(15) and validate our use of duplex sequencing for the detection of UV-induced mutagenesis. We chose to carry out subsequent experiments using UVC because UVB and UVC produce similar mutagenic photoproducts.…”

Section: Significancesupporting

confidence: 93%

“…3B). These results are consistent with previous reports, using reporter genes, of elevated UV-induced mutagenesis in XP cells (11). Additionally, normal cells showed a smaller, shallow increase in UV-specific mutations with UVC dose, as is consistent with efficient repair that minimizes UV-induced mutations and skin cancer initiation in repair-proficient cells (10).…”

Section: Uvc Induces An Elevated Subclonal Mutation Frequency In Xp-csupporting

confidence: 93%

“…Maher showed that UV-induced mutations in the hypoxanthine phosphoribosyl transferase (HPRT) gene that conferred resistance to 6-thioguanine (6-TG) were greatly enhanced in XP cells from both excision-defective and polymerase-defective groups (11,12). Similar studies in CS cells, however, failed to show an increase in UV-induced mutations in HPRT, T-cell receptor, or glycophorin A gene loci (13).…”

mentioning

confidence: 97%

“…However, in stark contrast to the dramatic increase in skin cancer incidence in XP-C patients, no CS patient has ever been reported to develop cancer, skin or otherwise (1,(4)(5)(6)(7)(8). Because cancer, especially in skin, is associated with mutagenesis (9, 10), we hypothesized that, unlike defects in GGR, which are associated with enhanced UV-induced mutagenesis in XP-C cells (11), the TCR defects in CS cells may not lead to increased mutagenicity.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Why Cockayne syndrome patients do not get cancer despite their DNA repair deficiency

Reid-Bayliss

Arron

Loeb

et al. 2016

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

View full text Add to dashboard Cite

Cockayne syndrome (CS) and xeroderma pigmentosum (XP) are human photosensitive diseases with mutations in the nucleotide excision repair (NER) pathway, which repairs DNA damage from UV exposure. CS is mutated in the transcription-coupled repair (TCR) branch of the NER pathway and exhibits developmental and neurological pathologies. The XP-C group of XP patients have mutations in the global genome repair (GGR) branch of the NER pathway and have a very high incidence of UV-induced skin cancer. Cultured cells from both diseases have similar sensitivity to UV-induced cytotoxicity, but CS patients have never been reported to develop cancer, although they often exhibit photosensitivity. Because cancers are associated with increased mutations, especially when initiated by DNA damage, we examined UV-induced mutagenesis in both XP-C and CS cells, using duplex sequencing for high-sensitivity mutation detection. Duplex sequencing detects rare mutagenic events, independent of selection and in multiple loci, enabling examination of all mutations rather than just those that confer major changes to a specific protein. We found telomerase-positive normal and CS-B cells had increased background mutation frequencies that decreased upon irradiation, purging the population of subclonal variants. Primary XP-C cells had increased UV-induced mutation frequencies compared with normal cells, consistent with their GGR deficiency. CS cells, in contrast, had normal levels of mutagenesis despite their TCR deficiency. The lack of elevated UV-induced mutagenesis in CS cells reveals that their TCR deficiency, although increasing cytotoxicity, is not mutagenic. Therefore the absence of cancer in CS patients results from the absence of UV-induced mutagenesis rather than from enhanced lethality.

show abstract

Section: Significancesupporting

confidence: 93%

Section: Uvc Induces An Elevated Subclonal Mutation Frequency In Xp-csupporting

confidence: 93%

mentioning

confidence: 97%

mentioning

confidence: 99%

See 2 more Smart Citations

Why Cockayne syndrome patients do not get cancer despite their DNA repair deficiency

Reid-Bayliss

Arron

Loeb

et al. 2016

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

View full text Add to dashboard Cite

show abstract

“…For example, xeroderma pigmentosum (XP) 4 patients possess inherited defects in nucleotide excision repair (NER) and a predilection to skin cancer, and the mutation rate is significantly elevated in their cells when exposed to UV light (Maher et al, 1979). Cells from hereditary non-polyposis colorectal cancer (HNPCC) associated cancers and sporadic colorectal cancer (CRCs), possess a mutator phenotype that arises from genetic or epigenetic defects in the DNA mismatch repair (MMR) system (Fishel et al, 1993;Leach et al, 1993;Kane et al, 1997;Veigl et al, 1998).…”

mentioning

confidence: 99%

A subgroup of microsatellite stable colorectal cancers has elevated mutation rates and different responses to alkylating and oxidising agents

Parker

Leonard

et al. 2004

Br J Cancer

View full text Add to dashboard Cite

An early step in the carcinogenesis of hereditary non-polyposis colorectal cancer (HNPCC) and some sporadic colorectal cancers (CRCs) is the acquisition of a 'mutator phenotype' resulting from defects in DNA mismatch repair (MMR) genes, which normally maintain genomic stability. This mutator phenotype causes an approximately 100 -1000-fold increase in base substitutions and small insertion/deletion mutations thereby driving carcinogenesis. It also causes genome-wide microsatellite instability (MSI) due to the inability to repair mutations within these small, hard to replicate, repetitive DNA elements. In contrast, less is known about the role of mutator phenotypes in microsatellite stable (MSS) CRC. In this report, we have measured the mutation rates in 11 MSS CRC cell lines to obtain an estimate of the prevalence of mutator phenotypes in MSS carcinogenesis. Of the 11 cell lines, three of them (27%) possess spontaneous hypoxanthine phosphoribosyltransferase mutation rates approximately 10 -100-fold above background. When challenged with alkylating and oxidising agents, the degree of survival and apoptotic responses are different, indicating that these cell lines may represent more than one mutator phenotype. These data demonstrate that a significant portion of MSS CRC cell lines has increased mutation rates and that this may play a role in MSS CRC carcinogenesis.

show abstract

Nickel subsulfide is similar to potassium dichromate in protecting normal human fibroblasts from the mutagenic effects of benzo[a]pyrene diolepoxide

Hamdan¹,

Morse²,

Reinhold³

1999

Environ. Mol. Mutagen.

View full text Add to dashboard Cite

DNA excision-repair processes in human cells can eliminate the cytotoxic and mutagenic consequences of ultraviolet irradiation

Cited by 236 publications

References 15 publications

Why Cockayne syndrome patients do not get cancer despite their DNA repair deficiency

Why Cockayne syndrome patients do not get cancer despite their DNA repair deficiency

A subgroup of microsatellite stable colorectal cancers has elevated mutation rates and different responses to alkylating and oxidising agents

Nickel subsulfide is similar to potassium dichromate in protecting normal human fibroblasts from the mutagenic effects of benzo[a]pyrene diolepoxide

Contact Info

Product

Resources

About