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Functional interplay between the oxidative stress response and DNA damage checkpoint signaling for genome maintenance in aerobic organisms

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Abstract

The DNA damage checkpoint signaling pathway is a highly conserved surveillance mechanism that ensures genome integrity by sequential activation of protein kinase cascades. In mammals, the main pathway is orchestrated by two central sensor kinases, ATM and ATR, that are activated in response to DNA damage and DNA replication stress. Patients lacking functional ATM or ATR suffer from ataxia-telangiectasia (A-T) or Seckel syndrome, respectively, with pleiotropic degenerative phenotypes. In addition to DNA strand breaks, ATM and ATR also respond to oxidative DNA damage and reactive oxygen species (ROS), suggesting an unconventional function as regulators of intracellular redox status. Here, we summarize the multiple roles of ATM and ATR, and of their orthologs in Saccharomyces cerevisiae, Tel1 and Mec1, in DNA damage checkpoint signaling and the oxidative stress response, and discuss emerging ideas regarding the possible mechanisms underlying the elaborate crosstalk between those pathways. This review may provide new insights into the integrated cellular strategies responsible for maintaining genome stability in eukaryotes with a focus on the yeast model organism.

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References

  • Alexander, A., Cai, S.L., Kim, J., Nanez, A., Sahin, M., MacLean, K.H., Inoki, K., Guan, K.L., Shen, J., Person, M.D., et al. 2010. ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response to ROS. Proc. Natl. Acad. Sci. USA107, 4153–4158.

    CAS  PubMed  Google Scholar 

  • Awasthi, P., Foiani, M., and Kumar, A. 2015. ATM and ATR signaling at a glance. J. Cell Sci.128, 4255–4262.

    CAS  PubMed  Google Scholar 

  • Bakkenist, C.J. and Kastan, M.B. 2003. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature421, 499–506.

    CAS  PubMed  Google Scholar 

  • Baldo, V., Testoni, V., Lucchini, G., and Longhese, M.P. 2008. Dominant TELl-hy mutations compensate for Mec1 lack of functions in the DNA damage response. Mol. Cell. Biol.28, 358–375.

    CAS  PubMed  Google Scholar 

  • Barzilai, A., Rotman, G., and Shiloh, Y. 2002. ATM deficiency and oxidative stress: a new dimension of defective response to DNA damage. DNA Repair (Amst)1, 3–25.

    CAS  Google Scholar 

  • Bencokova, Z., Kaufmann, M.R., Pires, I.M., Lecane, P.S., Giaccia, A.J., and Hammond, E.M. 2009. ATM activation and signalling under hypoxic conditions. Mol. Cell. Biol.29, 526–537.

    CAS  PubMed  Google Scholar 

  • Brown, E.J. and Baltimore, D. 2000. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev.14, 397–402.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bruner, S.D., Norman, D.P., and Verdine, G.L. 2000. Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature403, 859–866.

    CAS  PubMed  Google Scholar 

  • Burma, S., Chen, B.P., Murphy, M., Kurimasa, A., and Chen, D.J. 2001. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J. Biol. Chem.276, 42462–42467.

    CAS  PubMed  Google Scholar 

  • Cadet, J., Davies, K.J.A., Medeiros, M.H., Di Mascio, P., and Wagner, J.R. 2017. Formation and repair of oxidatively generated damage in cellular DNA. Free Radic. Biol. Med.107, 13–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Carter, C.D., Kitchen, L.E., Au, W.C., Babic, C.M., and Basrai, M.A. 2005. Loss of SOD1 and LYS7 sensitizes Saccharomyces cerevisiae to hydroxyurea and DNA damage agents and downregulates MEC1 pathway effectors. Mol. Cell. Biol.25, 10273–10285.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chabes, A., Georgieva, B., Domkin, V., Zhao, X., Rothstein, R., and Thelander, L. 2003. Survival of DNA damage in yeast directly depends on increased dNTP levels allowed by relaxed feedback inhibition of ribonucleotide reductase. Cell112, 391–401.

    CAS  PubMed  Google Scholar 

  • Chen, W.T., Ebelt, N.D., Stracker, T.H., Xhemalce, B., Van Den Berg, C.L., and Miller, K.M. 2015. ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion. ELife4, e07270.

    PubMed Central  Google Scholar 

  • Chen, Y. and Sanchez, Y. 2004. Chk1 in the DNA damage response: conserved roles from yeasts to mammals. DNA Repair (Amst)3, 1025–1032.

    CAS  Google Scholar 

  • Cheng, A., Zhao, T., Tse, K.H., Chow, H.M., Cui, Y., Jiang, L., Du, S., Loy, M.M.T., and Herrup, K. 2018. ATM and ATR play complementary roles in the behavior of excitatory and inhibitory vesicle populations. Proc. Natl. Acad. Sci. USA115, E292–E301.

    CAS  PubMed  Google Scholar 

  • Choi, J.E. and Chung, W.H. 2019. Synthetic lethal interaction between oxidative stress response and DNA damage repair in the budding yeast and its application to targeted anticancer therapy. J. Microbiol.57, 9–17.

    CAS  PubMed  Google Scholar 

  • Choi, J.E., Heo, S.H., Kim, M.J., and Chung, W.H. 2018. Lack of superoxide dismutase in a rad51 mutant exacerbates genomic instability and oxidative stress-mediated cytotoxicity in Saccharomyces cerevisiae. Free Radic. Biol. Med.129, 97–106.

    CAS  PubMed  Google Scholar 

  • Chung, W.H. 2017. Unraveling new functions of superoxide dismutase using yeast model system: Beyond its conventional role in superoxide radical scavenging. J. Microbiol.55, 409–416.

    CAS  PubMed  Google Scholar 

  • Ciccia, A. and Elledge, S.J. 2010. The DNA damage response: making it safe to play with knives. Mol. Cell40, 179–204.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Clerici, M., Trovesi, C., Galbiati, A., Lucchini, G., and Longhese, M.P. 2014. Mec1/ATR regulates the generation of single-stranded DNA that attenuates Tel1/ATM signaling at DNA ends. EMBO J.33, 198–216.

    CAS  PubMed  Google Scholar 

  • Corcoles-Saez, I., Dong, K., Johnson, A.L., Waskiewicz, E., Costanzo, M., Boone, C., and Cha, R.S. 2018. Essential function of Mec1, the budding yeast ATM/ATR checkpoint-response kinase, in protein homeostasis. Dev. Cell46, 495–503.

    CAS  PubMed  Google Scholar 

  • Cortez, D., Guntuku, S., Qin, J., and Elledge, S.J. 2001. ATR and ATRIP: partners in checkpoint signaling. Science294, 1713–1716.

    CAS  PubMed  Google Scholar 

  • Cosentino, C., Grieco, D., and Costanzo, V. 2011. ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair. EMBO J.30, 546–555.

    CAS  PubMed  Google Scholar 

  • Craven, R.J., Greenwell, P.W., Dominska, M., and Petes, T.D. 2002. Regulation of genome stability by TEL1 and MEC1, yeast homologs of the mammalian ATM and ATR genes. Genetics161, 493–507.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Craven, R.J. and Petes, T.D. 2000. Involvement of the checkpoint protein Mec1p in silencing of gene expression at telomeres in Saccharomyces cerevisiae. Mol. Cell. Biol.20, 2378–2384.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dahl, E.S. and Aird, K.M. 2017. Ataxia-Telangiectasia mutated modulation of carbon metabolism in cancer. Front. Oncol.7, 291.

    PubMed  PubMed Central  Google Scholar 

  • Dantzer, F., Ménissier-de Murcia, J., Barlow, C., Wynshaw-Boris, A., and de Murcia, G. 1999. Poly(ADP-ribose) polymerase activity is not affected in ataxia telangiectasia cells and knockout mice. Carcinogenesis20, 177–180.

    CAS  PubMed  Google Scholar 

  • Desany, B.A., Alcasabas, A.A., Bachant, J.B., and Elledge, S.J. 1998. Recovery from DNA replicational stress is the essential function of the S-phase checkpoint pathway. Genes Dev.12, 2956–2970.

    CAS  PubMed  PubMed Central  Google Scholar 

  • de Klein, A., Muijtjens, M., van Os, R., Verhoeven, Y., Smit B., Carr, A.M., Lehmann, A.R., and Hoeijmakers, J.H. 2000. Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice. Curr. Biol.10, 479–482.

    CAS  PubMed  Google Scholar 

  • de Waard, H., de Wit, J., Andressoo, J.O., van Oostrom, C.T., Riis, B., Weimann, A., Poulsen, H.E., van Steeg, H., Hoeijmakers, J.H., and van der Horst, G.T. 2004. Different effects of CSA and CSB deficiency on sensitivity to oxidative DNA damage. Mol. Cell. Biol.24, 7941–7948.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Di Domenico, E.G., Romano, E., Del Porto, P., and Ascenzioni, F. 2014. Multifunctional role of ATM/Tel1 kinase in genome stability: from the DNA damage response to telomere maintenance. Biomed. Res. Int.2014, 787404.

    PubMed  PubMed Central  Google Scholar 

  • Douki, T., Martini, R., Ravanat, J.L., Turesky, R.J., and Cadet, J. 1997. Measurement of 2,6-diamino-4-hydroxy-5-formamidopy-rimidine and 8-oxo-7,8-dihydroguanine in isolated DNA exposed to gamma radiation in aqueous solution. Carcinogenesis18, 2385–2391.

    CAS  PubMed  Google Scholar 

  • Earp, C., Rowbotham, S., Merényi, G., Chabes, A., and Cha, R.S. 2015. S phase block following MEC1ATR inactivation occurs without severe dNTP depletion. Biol. Open4, 1739–1743.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ellison, V. and Stillman, B. 2003. Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5′ recessed DNA. PLoS Biol.1, E33.

    PubMed  PubMed Central  Google Scholar 

  • Evans, M.D., Dizdaroglu, M., and Cooke, M.S. 2004. Oxidative DNA damage and disease: induction, repair and significance. Mutat. Res.567, 1–61.

    CAS  PubMed  Google Scholar 

  • Fasullo, M. and Sun, M. 2008. UV but not X rays stimulate homologous recombination between sister chromatids and homologs in a Saccharomyces cerevisiae mec1 (ATR) hypomorphic mutant. Mutat. Res.648, 73–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fasullo, M., Tsaponina, O., Sun, M., and Chabes, A. 2010. Elevated dNTP levels suppress hyper-recombination in Saccharomyces cerevisiae S-phase checkpoint mutants. Nucleic Acids Res.38, 1195–1203.

    CAS  PubMed  Google Scholar 

  • Finn, K., Lowndes, N.F., and Grenon, M. 2012. Eukaryotic DNA damage checkpoint activation in response to double-strand breaks. Cell. Mol. Life Sci.69, 1447–1473.

    CAS  PubMed  Google Scholar 

  • Gellon, L., Barbey, R., Auffret van der Kemp, P., Thomas, D., and Boiteux, S. 2001. Synergism between base excision repair, mediated by the DNA glycosylases Ntg1 and Ntg2, and nucleotide excision repair in the removal of oxidatively damaged DNA bases in Saccharomyces cerevisiae. Mol. Genet. Genomics265, 1087–1096.

    CAS  PubMed  Google Scholar 

  • Gibson, S.L., Bindra, R.S., and Glazer, P.M. 2005. Hypoxia-induced phosphorylation of Chk2 in an ataxia telangiectasia mutated-dependent manner. Cancer Res.65, 10734–10741.

    CAS  PubMed  Google Scholar 

  • Glasauer, A. and Chandel, N.S. 2013. ROS. Curr. Biol.23, R100–R102.

    CAS  PubMed  Google Scholar 

  • Grandin, N. and Charbonneau, M. 2007. Mrc1, a non-essential DNA replication protein, is required for telomere end protection following loss of capping by Cdc13, Yku or telomerase. Mol. Genet. Genomics277, 685–699.

    CAS  PubMed  Google Scholar 

  • Guo, Z., Kozlov, S., Lavin, M.F., Person, M.D., and Paull, T.T. 2010. ATM activation by oxidative stress. Science330, 517–521.

    CAS  PubMed  Google Scholar 

  • Harrison, J.C. and Haber, J.E. 2006. Surviving the breakup: the DNA damage checkpoint. Annu. Rev. Genet.40, 209–235.

    CAS  PubMed  Google Scholar 

  • Hartlerode, A.J., Morgan, M.J., Wu, Y., Buis, J., and Ferguson, D.O. 2015. Recruitment and activation of the ATM kinase in the absence of DNA-damage sensors. Nat. Struct. Mol. Biol.22, 736–743.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hoch, N.C., Chen, E.S., Buckland, R., Wang, S.C., Fazio, A., Hammet, A., Pellicioli, A., Chabes, A., Tsai, M.D., and Heierhorst, J. 2013. Molecular basis of the essential S phase function of the Rad53 checkpoint kinase. Mol. Cell. Biol.33, 3202–3213.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hoeijmakers, J.H. 2009. DNA damage, aging, and cancer. N. Engl. J. Med.361, 1475–1485.

    CAS  PubMed  Google Scholar 

  • Huang, M.E. and Kolodner, R.D. 2005. A biological network in Saccharomyces cerevisiae prevents the deleterious effects of endogenous oxidative DNA damage. Mol. Cell17, 709–720.

    CAS  PubMed  Google Scholar 

  • Huang, M.E., Rio, A.G., Nicolas, A., and Kolodner, R.D. 2003. A genomewide screen in Saccharomyces cerevisiae for genes that suppress the accumulation of mutations. Proc. Natl. Acad. Sci. USA100, 11529–11534.

    CAS  PubMed  Google Scholar 

  • Huang, M., Zhou, Z., and Elledge, S.J. 1998. The DNA replication and damage checkpoint pathways induce transcription by inhibition of the Crt1 repressor. Cell94, 595–605.

    CAS  PubMed  Google Scholar 

  • Hunt, C.R., Pandita, R.K., Laszlo, A., Higashikubo, R., Agarwal, M., Kitamura, T., Gupta, A., Rief, N., Horikoshi, N., Baskaran, R., et al. 2007. Hyperthermia activates a subset of ataxia-telangiectasia mutated effectors independent of DNA strand breaks and heat shock protein 70 status. Cancer Res.67, 3010–3017.

    CAS  PubMed  Google Scholar 

  • Ito, K., Hirao, A., Arai, F., Matsuoka, S., Takubo, K., Hamaguchi, I., Nomiyama, K., Hosokawa, K., Sakurada, K., Nakagata, N., et al. 2004. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature431, 997–1002.

    CAS  PubMed  Google Scholar 

  • Jaehnig, E.J., Kuo, D., Hombauer, H., Ideker, T.G., and Kolodner, R.D. 2013. Checkpoint kinases regulate a global network of transcription factors in response to DNA damage. Cell Rep.4, 174–188.

    CAS  PubMed  Google Scholar 

  • Jazayeri, A., Balestrini, A., Garner, E., Haber, J.E., and Costanzo, V. 2008. Mre11-Rad50-Nbs1-dependent processing of DNA breaks generates oligonucleotides that stimulate ATM activity. EMBO J.27, 1953–1962.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jung, M., Zhang, Y., Lee, S., and Dritschilo, A. 1995. Correction of radiation sensitivity in ataxia telangiectasia cells by a truncated I kappa B-alpha. Science268, 1619–1621.

    CAS  PubMed  Google Scholar 

  • Kanu, N., Penicud, K., Hristova, M., Wong, B., Irvine, E., Plattner, F., Raivich, G., and Behrens, A. 2010. The ATM cofactor ATMIN protects against oxidative stress and accumulation of DNA damage in the aging brain. J. Biol. Chem.285, 38534–38542.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kastan, M.B. and Bartek, J. 2004. Cell-cycle checkpoints and cancer. Nature432, 316–323.

    CAS  PubMed  Google Scholar 

  • Kato, R. and Ogawa, H. 1994. An essential gene, ESR1, is required for mitotic cell growth, DNA repair and meiotic recombination in Saccharomyces cerevisiae. Nucleic Acids Res.22, 3104–3112.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Khanna, K.K. and Jackson, S.P. 2001. DNA double-strand breaks: signaling, repair and the cancer connection. Nat. Genet.27, 247–254.

    CAS  PubMed  Google Scholar 

  • Kirsch, M. and De Groot, H. 2001. NAD(P)H, a directly operating antioxidant? FASEB J.15, 1569–1574.

    CAS  PubMed  Google Scholar 

  • Komata, M., Bando, M., Araki, H., and Shirahige, K. 2009. The direct binding of Mrc1, a checkpoint mediator, to Mcm6, a replication helicase, is essential for the replication checkpoint against methyl methanesulfonate-induced stress. Mol. Cell. Biol.29, 5008–5019.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kryston, T.B., Georgiev, A.B., Pissis, P., and Georgakilas, A.G. 2011. Role of oxidative stress and DNA damage in human carcinogenesis. Mutat. Res.711, 193–201.

    CAS  PubMed  Google Scholar 

  • Kulkarni, A. and Das, K.C. 2008. Differential roles of ATR and ATM in p53, Chk1, and histone H2AX phosphorylation in response to hyperoxia: ATR-dependent ATM activation. Am. J. Physiol. Lung Cell. Mol. Physiol.294, L998–L1006.

    CAS  PubMed  Google Scholar 

  • Lee, J.H. and Paull, T.T. 2005. ATM activation by DNA doublestrand breaks through the Mre11-Rad50-Nbs1 complex. Science308, 551–554.

    CAS  PubMed  Google Scholar 

  • Lee, Y.D., Wang, J., Stubbe, J., and Elledge, S.J. 2008. Dif1 is a DNA-damage regulated facilitator of nuclear import for ribonucleotide reductase. Mol. Cell32, 70–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lempiäinen, H. and Halazonetis, T.D. 2009. Emerging common themes in regulation of PIKKs and PI3Ks. EMBO J.28, 3067–3073.

    PubMed  PubMed Central  Google Scholar 

  • Lopes, M., Cotta-Ramusino, C., Pellicioli, A., Liberi, G., Plevani, P., Muzi-Falconi, M., Newlon, C.S., and Foiani, M. 2001. The DNA replication checkpoint response stabilizes stalled replication forks. Nature412, 557–561.

    CAS  PubMed  Google Scholar 

  • Lou, H., Komata, M., Katou, Y., Guan, Z., Reis, C.C., Budd, M., Shirahige, K., and Campbell, J.L. 2008. Mrc1 and DNA polymer- ase epsilon function together in linking DNA replication and the S phase checkpoint. Mol. Cell32, 106–117.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mallory, J.C. and Petes, T.D. 2000. Protein kinase activity of Tel1p and Mec1p, two Saccharomyces cerevisiae proteins related to the human ATM protein kinase. Proc. Natl. Acad. Sci. USA97, 13749–13754.

    CAS  PubMed  Google Scholar 

  • Mantiero, D., Clerici, M., Lucchini, G., and Longhese, M.P. 2007. Dual role for Saccharomyces cerevisiae Tel1 in the checkpoint response to double-strand breaks. EMBO Rep.8, 380–387.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Maréchal, A. and Zou, L. 2013. DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb. Perspect. Biol.5, a012716.

    PubMed  PubMed Central  Google Scholar 

  • Marnett, L.J. 2000. Oxyradicals and DNA damage. Carcinogenesis21, 361–370.

    CAS  PubMed  Google Scholar 

  • Matsuoka, S., Ballif, B.A., Smogorzewska, A., McDonald, E.R.3rd, Hurov, K.E., Luo, J., Bakalarski, C.E., Zhao, Z., Solimini, N., Lerenthal, Y., et al. 2007. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science316, 1160–1166.

    CAS  PubMed  Google Scholar 

  • Melis, J.P., van Steeg, H., and Luijten, M. 2013. Oxidative DNA damage and nucleotide excision repair. Antioxid. Redox Signal.18, 2409–2419.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Moyal, L., Lerenthal, Y., Gana-Weisz, M., Mass, G., So, S., Wang, S.Y., Eppink, B., Chung, Y.M., Shalev, G., Shema, E., et al. 2011. Requirement of ATM-dependent monoubiquitylation of histone H2B for timely repair of DNA double-strand breaks. Mol. Cell41, 529–542.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Naiki, T., Wakayama, T., Nakada, D., Matsumoto, K., and Sugimoto, K. 2004. Association of Rad9 with double-strand breaks through a Mec1-dependent mechanism. Mol. Cell. Biol.24, 3277–3285.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Oberle, C. and Blattner, C. 2010. Regulation of the DNA damage response to DSBs by post-translational modifications. Curr. Genomics11, 184–198.

    CAS  PubMed  PubMed Central  Google Scholar 

  • O’Driscoll, M., Ruiz-Perez, V.L., Woods, C.G., Jeggo, P.A., and Goodship, J.A. 2003. A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome. Nat. Genet.33, 497–501.

    PubMed  Google Scholar 

  • Ogi, T., Walker, S., Stiff, T., Hobson, E., Limsirichaikul, S., Carpenter, G., Prescott, K., Suri, M., Byrd, P.J., Matsuse, M., et al. 2012. Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome. PLoS Genet.8, e1002945.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Oh, J., Al-Zain, A., Cannavo, E., Cejka, P., and Symington, L.S. 2016. Xrs2 dependent and independent functions of the Mre11-Rad50 complex. Mol. Cell64, 405–415.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Okuno, Y., Nakamura-Ishizu, A., Otsu, K., Suda, T., and Kubota, Y. 2012. Pathological neoangiogenesis depends on oxidative stress regulation by ATM. Nat. Med.18, 1208–1216.

    CAS  PubMed  Google Scholar 

  • Osborn, A.J. and Elledge, S.J. 2003. Mrc1 is a replication fork component whose phosphorylation in response to DNA replication stress activates Rad53. Genes Dev.17, 1755–1767.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Paciotti, V., Clerici, M., Lucchini, G., and Longhese, M.P. 2000. The checkpoint protein Ddc2, functionally related to S. pombe Rad26, interacts with Mec1 and is regulated by Mec1-dependent phosphorylation in budding yeast. Genes Dev.14, 2046–2059.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pascucci, B., Lemma, T., Iorio, E., Giovannini, S., Vaz, B., Iavarone, I., Calcagnile, A., Narciso, L., Degan, P., Podo, F., et al. 2012. An altered redox balance mediates the hypersensitivity of Cockayne syndrome primary fibroblasts to oxidative stress. Aging Cell11, 520–529.

    CAS  PubMed  Google Scholar 

  • Reichenbach, J., Schubert, R., Schindler, D., Müller, K., Böhles, H., and Zielen, S. 2002. Elevated oxidative stress in patients with ataxia telangiectasia. Antioxid. Redox Signal.4, 465–469.

    CAS  PubMed  Google Scholar 

  • Rotman, G. and Shiloh, Y. 1997. Ataxia-telangiectasia: is ATM a sensor of oxidative damage and stress? Bioessays19, 911–917.

    CAS  PubMed  Google Scholar 

  • Sajesh, B.V., Bailey, M., Lichtensztejn, Z., Hieter, P., and McManus, K.J. 2013. Synthetic lethal targeting of superoxide dismutase 1 selectively kills RAD54B-deficient colorectal cancer cells. Genetics195, 757–767.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sajesh, B.V. and McManus, K.J. 2015. Targeting SOD1 induces synthetic lethal killing in BLM- and CHEK2-deficient colorectal cancer cells. Oncotarget.6, 27907–27922.

    PubMed  PubMed Central  Google Scholar 

  • Savitsky, K., Bar-Shira, A., Gilad, S., Rotman, G., Ziv, Y., Vanagaite, L., Tagle, D.A., Smith, S., Uziel, T., Sfez, S., et al. 1995. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science268, 1749–1753.

    CAS  PubMed  Google Scholar 

  • Shackelford, R.E., Innes, C.L., Sieber, S.O., Heinloth, A.N., Leadon, S.A., and Paules, R.S. 2001. The Ataxia telangiectasia gene product is required for oxidative stress-induced G1 and G2 checkpoint function in human fibroblasts. J. Biol. Chem.276, 21951–21959.

    CAS  PubMed  Google Scholar 

  • Shechter, D., Costanzo, V., and Gautier, J. 2004. ATR and ATM regulate the timing of DNA replication origin firing. Nat. Cell Biol.6, 648–655.

    CAS  PubMed  Google Scholar 

  • Shiloh, Y. 2003. ATM and related protein kinases: safeguarding genome integrity. Nat. Rev. Cancer3, 155–168.

    CAS  PubMed  Google Scholar 

  • Shiloh, Y. and Kastan, M.B. 2001. ATM: genome stability, neuronal development, and cancer cross paths. Adv. Cancer Res.83, 209–254.

    CAS  PubMed  Google Scholar 

  • Shiloh, Y. and Ziv, Y. 2013. The ATM protein kinase: regulating the cellular response to genotoxic stress, and more. Nat. Rev. Mol. Cell Biol.14, 197–210.

    CAS  PubMed  Google Scholar 

  • Shiotani, B. and Zou, L. 2009. Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks. Mol. Cell33, 547–558.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Slupphaug, G., Kavli, B., and Krokan, H.E. 2003. The interacting pathways for prevention and repair of oxidative DNA damage. Mutat. Res.531, 231–251.

    CAS  PubMed  Google Scholar 

  • Stracker, T.H., Usui, T., and Petrini, J.H. 2009. Taking the time to make important decisions: the checkpoint effector kinases Chk1 and Chk2 and the DNA damage response. DNA Repair (Amst)8, 1047–1054.

    CAS  Google Scholar 

  • Stucki, M., Clapperton, J.A., Mohammad, D., Yaffe, M.B., Smerdon, S.J., and Jackson, S.P. 2005. MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell123, 1213–1226.

    CAS  PubMed  Google Scholar 

  • Takata, H., Kanoh, Y., Gunge, N., Shirahige, K., and Matsuura, A. 2004. Reciprocal association of the budding yeast ATM-related proteins Tel1 and Mec1 with telomeres in vivo. Mol. Cell14, 515–522.

    CAS  PubMed  Google Scholar 

  • Tanny, J.C. and Moazed, D. 2001. Coupling of histone deacetylation to NAD breakdown by the yeast silencing protein Sir2: Evidence for acetyl transfer from substrate to an NAD breakdown product. Proc. Natl. Acad. Sci. USA98, 415–420.

    CAS  PubMed  Google Scholar 

  • Tercero, J.A., Longhese, M.P., and Diffley, J.F. 2003. A central role for DNA replication forks in checkpoint activation and response. Mol. Cell11, 1323–1336.

    CAS  PubMed  Google Scholar 

  • Thaminy, S., Newcomb, B., Kim, J., Gatbonton, T., Foss, E., Simon, J., and Bedalov, A. 2007. Hst3 is regulated by Mec1-dependent proteolysis and controls the S phase checkpoint and sister chromatid cohesion by deacetylating histone H3 at lysine 56. J. Biol. Chem.282, 37805–37814.

    CAS  PubMed  Google Scholar 

  • Thorslund, T., von Kobbe, C., Harrigan, J.A., Indig, F.E., Christiansen, M., Stevnsner, T., and Bohr, V.A. 2005. Cooperation of the Cockayne syndrome group B protein and poly(ADP-ribose) polymerase 1 in the response to oxidative stress. Mol. Cell. Biol.25, 7625–7636.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tsang, C.K., Liu, Y., Thomas, J., Zhang, Y., and Zheng, X.F. 2014. Superoxide dismutase 1 acts as a nuclear transcription factor to regulate oxidative stress resistance. Nat. Commun.5, 3446.

    PubMed  PubMed Central  Google Scholar 

  • Uziel, T., Lerenthal, Y., Moyal, L., Andegeko, Y., Mittelman, L., and Shiloh, Y. 2003. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J.22, 5612–5621.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Valentin-Vega, Y.A., Maclean, K.H., Tait-Mulder, J., Milasta, S., Steeves, M., Dorsey, F.C., Cleveland, J.L., Green, D.R., and Kastan, M.B. 2012. Mitochondrial dysfunction in ataxia-telangiectasia. Blood119, 1490–1500.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Vialard, J.E., Gilbert, C.S., Green, C.M., and Lowndes, N.F. 1998. The budding yeast Rad9 checkpoint protein is subjected to Mec1/ Tel1-dependent hyperphosphorylation and interacts with Rad53 after DNA damage. EMBO J.17, 5679–5688.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Weinert, T.A., Kiser, G.L., and Hartwell, L.H. 1994. Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Genes Dev.8, 652–665.

    CAS  PubMed  Google Scholar 

  • Willis, J., Patel, Y., Lentz, B.L., and Yan, S. 2013. APE2 is required for ATR-Chk1 checkpoint activation in response to oxidative stress. Proc. Natl. Acad. Sci. USA110, 10592–10597.

    CAS  PubMed  Google Scholar 

  • Yan, S., Sorrell, M., and Berman, Z. 2014. Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress. Cell. Mol. Life Sci.71, 3951–3967.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang, D.Q. and Kastan, M.B. 2000. Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1. Nat. Cell Biol.2, 893–898.

    CAS  PubMed  Google Scholar 

  • Yi, D.G., Kim, M.J., Choi, J.E., Lee, J., Jung, J., Huh, W.K., and Chung, W.H. 2016. Yap1 and Skn7 genetically interact with Rad51 in response to oxidative stress and DNA double-strand break in Saccharomyces cerevisiae. Free Radic. Biol. Med.101, 424–433.

    CAS  PubMed  Google Scholar 

  • You, Z., Chahwan, C., Bailis, J., Hunter, T., and Russell, P. 2005. ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1. Mol. Cell. Biol.25, 5363–5379.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, D., Hu, X., Li, J., Liu, J., Baks-Te Bulte, L., Wiersma, M., Malik, N.U., van Marion, D.M.S., Tolouee, M., Hoogstra-Berends, F., et al. 2019a. DNA damage-induced PARP1 activation confers cardiomyocyte dysfunction through NAD+ depletion in experimental atrial fibrillation. Nat. Commun.10, 1307.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, Y. and Hunter, T. 2014. Roles of Chk1 in cell biology and cancer therapy. Int. J. Cancer134, 1013–1023.

    CAS  PubMed  Google Scholar 

  • Zhang, T., Penicud, K., Bruhn, C., Loizou, J.I., Kanu, N., Wang, Z.Q., and Behrens, A. 2012. Competition between NBS1 and ATMIN controls ATM signaling pathway choice. Cell Rep.2, 1498–1504.

    CAS  PubMed  Google Scholar 

  • Zhang, K., Zheng, D.Q., Sui, Y., Qi, L., and Petes, T.D. 2019b. Genome-wide analysis of genomic alterations induced by oxidative DNA damage in yeast. Nucleic Acids Res.47, 3521–3535.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao, X., Chabes, A., Domkin, V., Thelander, L., and Rothstein, R. 2001. The ribonucleotide reductase inhibitor Sml1 is a new target of the Mec1/Rad53 kinase cascade during growth and in response to DNA damage. EMBO J.20, 3544–3553.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao, X., Muller, E.G., and Rothstein, R. 1998. A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools. Mol. Cell2, 329–340.

    CAS  PubMed  Google Scholar 

  • Zhao, X. and Rothstein, R. 2002. The Dun1 checkpoint kinase phosphorylates and regulates the ribonucleotide reductase inhibitor Sml1. Proc. Natl. Acad. Sci. USA99, 3746–3751.

    CAS  PubMed  Google Scholar 

  • Zhou, Z. and Elledge, S.J. 1993. DUN1 encodes a protein kinase that controls the DNA damage response in yeast. Cell75, 1119–1127.

    CAS  PubMed  Google Scholar 

  • Zhou, B.B. and Elledge, S.J. 2000. The DNA damage response: putting checkpoints in perspective. Nature408, 433–439.

    CAS  PubMed  Google Scholar 

  • Zou, L. and Elledge, S.J. 2003. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science300, 1542–1548.

    CAS  PubMed  Google Scholar 

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Acknowledgments

The work for this review was supported by the Duksung Women’s University Research Grants 2017.

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  1. College of Pharmacy, Duksung Women’s University, Seoul, 01369, Republic of Korea

    Ji Eun Choi & Woo-Hyun Chung

  2. Innovative Drug Center, Duksung Women’s University, Seoul, 01369, Republic of Korea

    Ji Eun Choi & Woo-Hyun Chung

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Choi, J.E., Chung, WH. Functional interplay between the oxidative stress response and DNA damage checkpoint signaling for genome maintenance in aerobic organisms. J Microbiol. 58, 81–91 (2020). https://doi.org/10.1007/s12275-020-9520-x

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