Oxidative Damage to RPA Limits the Nucleotide Excision Repair Capacity of Human Cells

Guven, Melisa; Brem, Reto; Macpherson, Peter; Peacock, Matthew; Karran, Peter

doi:10.1038/jid.2015.255

Cited by 56 publications

(50 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…UVA‐DDR compared to UVB and UVC light was previously reported. Poor UVA‐DDR induction when compared to UVC could be due to extensive oxidation of proteins as a result of UVA exposure , as well as specific oxidation of proteins related to DNA repair and TLS, such as RPA and PCNA . Therefore, the DDR proteins with impaired functions could justify lower induction compared to UVC, since the reduction in active RPA and PCNA could be an aggravating factor for TLS in XP‐V patients .…”

Section: Discussionmentioning

confidence: 99%

“…UVA light may cause DNA damage through direct absorption of photons by nitrogenous bases, thereby giving rise to pyrimidine dimers, such as cyclobutane pyrimidine (CPD), pyrimidine (6‐4) and pyrimidone (6‐4 PP) . Moreover, it might also be detrimental through indirect mechanisms, such as photosensitization , or by late induction of the redox process associated to cellular metabolism , both leading to DNA and protein oxidation . Interestingly, the oxidation of melanin by UVA light was shown to also induce the formation of pyrimidine dimers 3 h after irradiation, known as dark CPDs .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

ATR/Chk1 Pathway is Activated by Oxidative Stress in Response to UVA Light in Human Xeroderma Pigmentosum Variant Cells

Moreno

García

Rocha

et al. 2018

Photochem & Photobiology

View full text Add to dashboard Cite

The crucial role of DNA polymerase eta in protecting against sunlight‐induced tumors is evidenced in Xeroderma Pigmentosum Variant (XP‐V) patients, who carry mutations in this protein and present increased frequency of skin cancer. XP‐V cellular phenotypes may be aggravated if proteins of DNA damage response (DDR) pathway are blocked, as widely demonstrated by experiments with UVC light and caffeine. However, little is known about the participation of DDR in XP‐V cells exposed to UVA light, the wavelengths patients are mostly exposed. Here, we demonstrate the participation of ATR kinase in protecting XP‐V cells after receiving low UVA doses using a specific inhibitor, with a remarkable increase in sensitivity and γH2AX signaling. Corroborating ATR participation in UVA‐DDR, a significant increase in Chk1 protein phosphorylation, as well as S‐phase cell cycle arrest, is also observed. Moreover, the participation of oxidative stress is supported by the antioxidant action of N‐acetylcysteine (NAC), which significantly protects XP‐V cells from UVA light, even in the presence of the ATR inhibitor. These findings indicate that the ATR/Chk1 pathway is activated to control UVA‐induced oxidatively generated DNA damage and emphasizes the role of ATR kinase as a mediator of genomic stability in pol eta defective cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ATR/Chk1 Pathway is Activated by Oxidative Stress in Response to UVA Light in Human Xeroderma Pigmentosum Variant Cells

Moreno

García

Rocha

et al. 2018

Photochem & Photobiology

View full text Add to dashboard Cite

show abstract

“…Recently, UVA has been shown to target OGG1 for oxidation and, in doing so, compromises BER of oxidized DNA . Furthermore, UVA has been shown to cause oxidative damage to single‐strand DNA‐binding factor RPA, impairing NER . This work suggests that there are combinatorial effects of UVA and UVB in inducing and perpetuating DNA damage.…”

Section: Autophagy In Oxidative Stress Responsementioning

confidence: 98%

Autophagy in UV Damage Response

Sample

2017

Photochem & Photobiology

View full text Add to dashboard Cite

UV radiation exposure from sunlight and artificial tanning beds is the major risk factor for the development of skin cancer and skin photoaging. UV-induced skin damage can trigger a cascade of DNA damage response signaling pathways, including cell cycle arrest, DNA repair, and, if damage is irreparable, apoptosis. Compensatory proliferation replaces the apoptotic cells to maintain skin barrier integrity. Disruption of these processes can be exploited to promote carcinogenesis by allowing the survival and proliferation of damaged cells. UV radiation also induces autophagy, a catabolic process that clears unwanted or damaged proteins, lipids, and organelles. The mechanisms by which autophagy is activated following UV exposure, and the functions of autophagy in UV response are only now being clarified. Here, we summarize the current understanding of the mechanisms governing autophagy regulation by UV, the roles of autophagy in regulating cellular response to UV-induced photodamage, and the implications of autophagy modulation in the treatment and prevention of photoaging and skin cancer.

show abstract

“…4 The combination of DNA 6-TG and UVA also induces protein damage in the form of carbonyls and oxidized thiols. 12 It causes oxidation-related cross-linking between the subunits of multiprotein complexes including the PCNA, 13 Ku, 12 RPA, 14 and MCM2–7 DNA replication/repair complexes 15 and between DNA and proteins. 3 Importantly, protein damage induced by 6-TG+UVA is associated with a significant attenuation of DNA repair capacity.…”

Section: Introductionmentioning

confidence: 99%

“…16 UVA irradiation of cells treated with ciprofloxacin causes damage to DNA and proteins. 17 Protein damage by ciprofloxacin+UVA also includes oxidation and cross-linking between subunits of DNA replication and repair complexes 14,17 and is associated with impaired DNA repair. 17 To our knowledge, the possible induction of DPCs by UVA-activated ciprofloxacin has not been examined.…”

Section: Introductionmentioning

confidence: 99%

Photosensitized UVA-Induced Cross-Linking between Human DNA Repair and Replication Proteins and DNA Revealed by Proteomic Analysis

et al. 2016

Self Cite

View full text Add to dashboard Cite

Long wavelength ultraviolet radiation (UVA, 320–400 nm) interacts with chromophores present in human cells to induce reactive oxygen species (ROS) that damage both DNA and proteins. ROS levels are amplified, and the damaging effects of UVA are exacerbated if the cells are irradiated in the presence of UVA photosensitizers such as 6-thioguanine (6-TG), a strong UVA chromophore that is extensively incorporated into the DNA of dividing cells, or the fluoroquinolone antibiotic ciprofloxacin. Both DNA-embedded 6-TG and ciprofloxacin combine synergistically with UVA to generate high levels of ROS. Importantly, the extensive protein damage induced by these photosensitizer+UVA combinations inhibits DNA repair. DNA is maintained in intimate contact with the proteins that effect its replication, transcription, and repair, and DNA–protein cross-links (DPCs) are a recognized reaction product of ROS. Cross-linking of DNA metabolizing proteins would compromise these processes by introducing physical blocks and by depleting active proteins. We describe a sensitive and statistically rigorous method to analyze DPCs in cultured human cells. Application of this proteomics-based analysis to cells treated with 6-TG+UVA and ciprofloxacin+UVA identified proteins involved in DNA repair, replication, and gene expression among those most vulnerable to cross-linking under oxidative conditions.

show abstract

Oxidative Damage to RPA Limits the Nucleotide Excision Repair Capacity of Human Cells

Cited by 56 publications

References 29 publications

ATR/Chk1 Pathway is Activated by Oxidative Stress in Response to UVA Light in Human Xeroderma Pigmentosum Variant Cells

ATR/Chk1 Pathway is Activated by Oxidative Stress in Response to UVA Light in Human Xeroderma Pigmentosum Variant Cells

Autophagy in UV Damage Response

Photosensitized UVA-Induced Cross-Linking between Human DNA Repair and Replication Proteins and DNA Revealed by Proteomic Analysis

Contact Info

Product

Resources

About