Abstract
To maintain genome stability, cells have evolved various DNA repair pathways to deal with oxidative DNA damage. DNA damage response (DDR) pathways, including ATM-Chk2 and ATR-Chk1 checkpoints, are also activated in oxidative stress to coordinate DNA repair, cell cycle progression, transcription, apoptosis, and senescence. Several studies demonstrate that DDR pathways can regulate DNA repair pathways. On the other hand, accumulating evidence suggests that DNA repair pathways may modulate DDR pathway activation as well. In this review, we summarize our current understanding of how various DNA repair and DDR pathways are activated in response to oxidative DNA damage primarily from studies in eukaryotes. In particular, we analyze the functional interplay between DNA repair and DDR pathways in oxidative stress. A better understanding of cellular response to oxidative stress may provide novel avenues of treating human diseases, such as cancer and neurodegenerative disorders.
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Abbreviations
- 9-1-1 complex:
-
Rad9-Rad1-Hus1
- AP:
-
Apurinic/apyrimidinic
- APE1:
-
AP endonuclease 1
- APE2:
-
AP endonuclease 2
- A-T:
-
Ataxia-telangiectasia
- ATM:
-
A-T mutated
- ATR:
-
ATM- and Rad3-related
- BER:
-
Base excision repair
- Chk1:
-
Checkpoint kinase 1
- Chk2:
-
Checkpoint kinase 2
- DDR:
-
DNA damage response
- DSB:
-
Double-strand break
- GG-NER:
-
Global genome NER
- HR:
-
Homologous recombination
- Ku complex:
-
Ku70/Ku80
- MCM:
-
Minichromosome maintenance
- MMR:
-
Mismatch repair
- MRN complex:
-
Mre11-Rad50-Nbs1
- NER:
-
Nucleotide excision repair
- NHEJ:
-
Non-homologous end joining
- PCNA:
-
Proliferating cell nuclear antigen
- ROS:
-
Reactive oxygen species
- RPA:
-
Replication protein A
- SSB:
-
Single-strand break
- SSBR:
-
SSB repair
- ssDNA:
-
Single-stranded DNA
- TC-NER:
-
Transcription-coupled NER
- TDP1:
-
Tyrosyl-DNA phosphodiesterase 1
- γ-H2AX:
-
H2AX phosphorylation at Serine 139
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Acknowledgments
The research in the Yan lab is supported in part by funds provided by University of North Carolina at Charlotte and a Grant from the NIGMS/NIH (R15 GM101571). We apologize to our colleagues whose publications were not cited due to space limitations.
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Yan, S., Sorrell, M. & Berman, Z. Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress. Cell. Mol. Life Sci. 71, 3951–3967 (2014). https://doi.org/10.1007/s00018-014-1666-4
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DOI: https://doi.org/10.1007/s00018-014-1666-4