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Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress

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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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  1. Department of Biological Sciences, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC, 28223, USA

    Shan Yan & Zachary Berman

  2. J. Murrey Atkins Library, University of North Carolina at Charlotte, 9201 University City Blvd., Charlotte, NC, 28223, USA

    Melanie Sorrell

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  1. Shan Yan
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Correspondence to Shan Yan.

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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

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