Abstract
DNA damage response (DDR) is an intracellular pathway that senses and repairs damaged DNA. Proper regulation of this pathway is essential for maintaining genome stability and promoting cell survival. These repair mechanisms are regulated by multiple nuclear DNA damage repair enzymes, which can scan the DNA for problems and restore the DNA double helix structure. In addition to DDR-involved proteins located in cell nuclei, mitochondrial molecular machinery also coordinate this role; the mitochondria sense fluctuations in specific DNA damage signaling and subsequently activate the effector molecules and appropriate pathway. In this review, we summarized the latest scientific literature regarding molecular mechanisms of mitochondria-mediated stress responses in DNA damage signaling. Additionally, we have described future directions necessary for a comprehensive understanding of mitochondria-DDR signaling networks.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Addabbo, F., Montagnani, M., & Goligorsky, M. S. (2009). Mitochondria and reactive oxygen species. Hypertension, 53(6), 885–892. https://doi.org/10.1161/hypertensionaha.109.130054
Alemasova, E. E., & Lavrik, O. I. (2019). Poly(adp-ribosyl)ation by parp1: Reaction mechanism and regulatory proteins. Nucleic Acids Research, 47(8), 3811–3827. https://doi.org/10.1093/nar/gkz120
Ali, A. A. E., Timinszky, G., Arribas-Bosacoma, R., Kozlowski, M., Hassa, P. O., Hassler, M., & Oliver, A. W. (2012). The zinc-finger domains of parp1 cooperate to recognize DNA strand breaks. Nature Structural & Molecular Biology, 19(7), 685–692. https://doi.org/10.1038/nsmb.2335
Anderson, K. A., Green, M. F., Huynh, F. K., Wagner, G. R., & Hirschey, M. D. (2014). Snapshot: mammalian sirtuins. Cell, 159(4), 956-956.e951. https://doi.org/10.1016/j.cell.2014.10.045
Babbar, M., Basu, S., Yang, B., Croteau, D. L., & Bohr, V. A. (2020). Mitophagy and DNA damage signaling in human aging. Mechanisms of Ageing and Development, 186, 111207. https://doi.org/10.1016/j.mad.2020.111207
Badura, M., Braunstein, S., Zavadil, J., & Schneider, R. J. (2012). DNA damage and eif4g1 in breast cancer cells reprogram translation for survival and DNA repair mrnas. Proceedings of the National Academy of Sciences of the United States of America, 109(46), 18767–18772. https://doi.org/10.1073/pnas.1203853109
Baritaud, M., Cabon, L., Delavallee, L., Galan-Malo, P., Gilles, M. E., Brunelle-Navas, M. N., & Susin, S. A. (2012). Aif-mediated caspase-independent necroptosis requires atm and DNA-pk-induced histone h2ax ser139 phosphorylation. Cell Death & Disease, 3, e390. https://doi.org/10.1038/cddis.2012.120
Bhatia-Kissova, I., & Camougrand, N. (2013). Mitophagy is not induced by mitochondrial damage but plays a role in the regulation of cellular autophagic activity. Autophagy, 9(11), 1897–1899. https://doi.org/10.4161/auto.23979
Bian, C., Zhang, C., Luo, T., Vyas, A., Chen, S. H., Liu, C., & Yu, X. (2019). Nadp(+) is an endogenous parp inhibitor in DNA damage response and tumor suppression. Nature Communications, 10(1), 693. https://doi.org/10.1038/s41467-019-08530-5
Biton, S., & Ashkenazi, A. (2011). Nemo and rip1 control cell fate in response to extensive DNA damage via tnf-alpha feedforward signaling. Cell, 145(1), 92–103. https://doi.org/10.1016/j.cell.2011.02.023
Bouley, J., Saad, L., Grall, R., Schellenbauer, A., Biard, D., Paget, V., & Delic, J. (2015). A new phosphorylated form of ku70 identified in resistant leukemic cells confers fast but unfaithful DNA repair in cancer cell lines. Oncotarget, 6(29), 27980–28000. https://doi.org/10.18632/oncotarget.4735
Caldecott, K. W. (2008). Single-strand break repair and genetic disease. Nature Reviews Genetics, 9(8), 619–631. https://doi.org/10.1038/nrg2380
Canto, C., Menzies, K. J., & Auwerx, J. (2015). Nad(+) metabolism and the control of energy homeostasis: A balancing act between mitochondria and the nucleus. Cell Metabolism, 22(1), 31–53. https://doi.org/10.1016/j.cmet.2015.05.023
Chang, H., Li, J., Qu, K., Wan, Y., Liu, S., Zheng, W., & Liu, C. (2020). Crif1 overexpression facilitates tumor growth and metastasis through inducing ros/nfkappab pathway in hepatocellular carcinoma. Cell Death & Disease, 11(5), 332. https://doi.org/10.1038/s41419-020-2528-7
Chen, B., Xu, F., Gao, Y., Hu, G., Zhu, K., Lu, H., & Zhao, G. (2022). DNA damage-induced translocation of mitochondrial factor higd1a into the nucleus regulates homologous recombination and radio/chemo-sensitivity. Oncogene, 41(13), 1918–1930. https://doi.org/10.1038/s41388-022-02226-9
Chen, Q., Lei, J. H., Bao, J., Wang, H., Hao, W., Li, L., & Deng, C. X. (2020). Brca1 deficiency impairs mitophagy and promotes inflammasome activation and mammary tumor metastasis. Adv Sci (weinh), 7(6), 1903616. https://doi.org/10.1002/advs.201903616
Chung, H. K., Yi, Y. W., Jung, N. C., Kim, D., Suh, J. M., Kim, H., & Shong, M. (2003). Cr6-interacting factor 1 interacts with gadd45 family proteins and modulates the cell cycle. Journal of Biological Chemistry, 278(30), 28079–28088. https://doi.org/10.1074/jbc.M212835200
Covarrubias, A. J., Perrone, R., Grozio, A., & Verdin, E. (2021). Nad+ metabolism and its roles in cellular processes during ageing. Nature Reviews Molecular Cell Biology, 22(2), 119–141. https://doi.org/10.1038/s41580-020-00313-x
Dai, Y., & Grant, S. (2010). New insights into checkpoint kinase 1 in the DNA damage response signaling network. Clinical Cancer Research, 16(2), 376–383. https://doi.org/10.1158/1078-0432.CCR-09-1029
Dan, X., Babbar, M., Moore, A., Wechter, N., Tian, J., Mohanty, J. G., & Bohr, V. A. (2020). DNA damage invokes mitophagy through a pathway involving spata18. Nucleic Acids Research, 48(12), 6611–6623. https://doi.org/10.1093/nar/gkaa393
David, K. K., Sasaki, M., Yu, S. W., Dawson, T. M., & Dawson, V. L. (2006). Endog is dispensable in embryogenesis and apoptosis. Cell Death and Differentiation, 13(7), 1147–1155. https://doi.org/10.1038/sj.cdd.4401787
Dutta, C., Day, T., Kopp, N., van Bodegom, D., Davids, M. S., Ryan, J., & Weinstock, D. M. (2012). Bcl2 suppresses parp1 function and nonapoptotic cell death. Cancer Research, 72(16), 4193–4203. https://doi.org/10.1158/0008-5472.CAN-11-4204
Fang, E. F., Scheibye-Knudsen, M., Chua, K. F., Mattson, M. P., Croteau, D. L., & Bohr, V. A. (2016). Nuclear DNA damage signalling to mitochondria in ageing. Nature Reviews Molecular Cell Biology, 17(5), 308–321. https://doi.org/10.1038/nrm.2016.14
Fell, V. L., Walden, E. A., Hoffer, S. M., Rogers, S. R., Aitken, A. S., Salemi, L. M., & Schild-Poulter, C. (2016). Ku70 serine 155 mediates aurora b inhibition and activation of the DNA damage response. Science and Reports, 6, 37194. https://doi.org/10.1038/srep37194
Filomeni, G., De Zio, D., & Cecconi, F. (2015). Oxidative stress and autophagy: The clash between damage and metabolic needs. Cell Death and Differentiation, 22(3), 377–388. https://doi.org/10.1038/cdd.2014.150
Flick, F., & Luscher, B. (2012). Regulation of sirtuin function by posttranslational modifications. Frontiers in Pharmacology, 3, 29. https://doi.org/10.3389/fphar.2012.00029
Friedberg, E. C. (2003). DNA damage and repair. Nature, 421(6921), 436–440. https://doi.org/10.1038/nature01408
Friedberg, E. C. (2008). A brief history of the DNA repair field. Cell Research, 18(1), 3–7. https://doi.org/10.1038/cr.2007.113
Gross, A., & Katz, S. G. (2017). Non-apoptotic functions of bcl-2 family proteins. Cell Death and Differentiation, 24(8), 1348–1358. https://doi.org/10.1038/cdd.2017.22
Gruosso, T., Mieulet, V., Cardon, M., Bourachot, B., Kieffer, Y., Devun, F., & Mechta-Grigoriou, F. (2016). Chronic oxidative stress promotes h2ax protein degradation and enhances chemosensitivity in breast cancer patients. EMBO Molecular Medicine, 8(5), 527–549. https://doi.org/10.15252/emmm.201505891
Gueble, S. E., & Bindra, R. S. (2022). Oncometabolites as regulators of DNA damage response and repair. Seminars in Radiation Oncology, 32(1), 82–94. https://doi.org/10.1016/j.semradonc.2021.09.004
Guo, Q. Q., Wang, S. S., Zhang, S. S., Xu, H. D., Li, X. M., Guan, Y., & Cao, L. (2020). Atm-chk2-beclin 1 axis promotes autophagy to maintain ros homeostasis under oxidative stress. EMBO Journal, 39(10), e103111. https://doi.org/10.15252/embj.2019103111
Haince, J. F., McDonald, D., Rodrigue, A., Dery, U., Masson, J. Y., Hendzel, M. J., & Poirier, G. G. (2008). Parp1-dependent kinetics of recruitment of mre11 and nbs1 proteins to multiple DNA damage sites. Journal of Biological Chemistry, 283(2), 1197–1208. https://doi.org/10.1074/jbc.M706734200
Hayashi, T., Asano, Y., Shintani, Y., Aoyama, H., Kioka, H., Tsukamoto, O., & Takashima, S. (2015). Higd1a is a positive regulator of cytochrome c oxidase. Proceedings of the National Academy of Sciences of the United States of America, 112(5), 1553–1558. https://doi.org/10.1073/pnas.1419767112
Iacobazzi, V., & Infantino, V. (2014). Citrate—new functions for an old metabolite. Biological Chemistry, 395(4), 387–399. https://doi.org/10.1515/hsz-2013-0271
Iijima, K., Muranaka, C., Kobayashi, J., Sakamoto, S., Komatsu, K., Matsuura, S., & Tauchi, H. (2008). Nbs1 regulates a novel apoptotic pathway through bax activation. DNA Repair (amst), 7(10), 1705–1716. https://doi.org/10.1016/j.dnarep.2008.06.013
Jackson, S. P., & Bartek, J. (2009). The DNA-damage response in human biology and disease. Nature, 461(7267), 1071–1078. https://doi.org/10.1038/nature08467
Jeong, J., Juhn, K., Lee, H., Kim, S. H., Min, B. H., Lee, K. M., & Lee, K. H. (2007). Sirt1 promotes DNA repair activity and deacetylation of ku70. Experimental & Molecular Medicine, 39(1), 8–13. https://doi.org/10.1038/emm.2007.2
Jiang, J., Yang, E. S., Jiang, G., Nowsheen, S., Wang, H., Wang, T., & Xia, F. (2011). P53-dependent brca1 nuclear export controls cellular susceptibility to DNA damage. Cancer Research, 71(16), 5546–5557. https://doi.org/10.1158/0008-5472.CAN-10-3423
Jiang, Z., Jin, S., Yalowich, J. C., Brown, K. D., & Rajasekaran, B. (2010). The mismatch repair system modulates curcumin sensitivity through induction of DNA strand breaks and activation of g2-m checkpoint. Molecular Cancer Therapeutics, 9(3), 558–568. https://doi.org/10.1158/1535-7163.MCT-09-0627
Jiricny, J. (2013). Postreplicative mismatch repair. Cold Spring Harbor Perspectives in Biology, 5(4), a012633. https://doi.org/10.1101/cshperspect.a012633
Kang, J. W., Zhan, Z., Ji, G., Sang, Y., Zhou, D., Li, Y., & Cheng, T. (2021). Puma facilitates emi1-promoted cytoplasmic rad51 ubiquitination and inhibits DNA repair in stem and progenitor cells. Signal Transduction and Targeted Therapy, 6(1), 129. https://doi.org/10.1038/s41392-021-00510-w
Kang, M. H., & Reynolds, C. P. (2009). Bcl-2 inhibitors: Targeting mitochondrial apoptotic pathways in cancer therapy. Clinical Cancer Research, 15(4), 1126–1132. https://doi.org/10.1158/1078-0432.CCR-08-0144
Kim, H. J., Oh, G. S., Choe, S. K., Kwak, T. H., Park, R., & So, H. S. (2014). Nad(+) metabolism in age-related hearing loss. Aging and Disease, 5(2), 150–159. https://doi.org/10.14336/AD.2014.0500150
Lans, H., Marteijn, J. A., & Vermeulen, W. (2012). Atp-dependent chromatin remodeling in the DNA-damage response. Epigenetics & Chromatin, 5(1), 4. https://doi.org/10.1186/1756-8935-5-4
Laulier, C., Barascu, A., Guirouilh-Barbat, J., Pennarun, G., Le Chalony, C., Chevalier, F., & Lopez, B. S. (2011). Bcl-2 inhibits nuclear homologous recombination by localizing brca1 to the endomembranes. Cancer Research, 71(10), 3590–3602. https://doi.org/10.1158/0008-5472.CAN-10-3119
Laulier, C., & Lopez, B. S. (2012). The secret life of bcl-2: Apoptosis-independent inhibition of DNA repair by bcl-2 family members. Mutation Research, 751(2), 247–257. https://doi.org/10.1016/j.mrrev.2012.05.002
Lee, J. H., Choy, M. L., Ngo, L., Foster, S. S., & Marks, P. A. (2010). Histone deacetylase inhibitor induces DNA damage, which normal but not transformed cells can repair. Proceedings of the National Academy of Sciences of the United States of America, 107(33), 14639–14644. https://doi.org/10.1073/pnas.1008522107
Li, G. M. (2008). Mechanisms and functions of DNA mismatch repair. Cell Research, 18(1), 85–98. https://doi.org/10.1038/cr.2007.115
Liu, C., Wu, J., Paudyal, S. C., You, Z., & Yu, X. (2013). Chfr is important for the first wave of ubiquitination at DNA damage sites. Nucleic Acids Research, 41(3), 1698–1710. https://doi.org/10.1093/nar/gks1278
Lozano, G., & Elledge, S. J. (2000). P53 sends nucleotides to repair DNA. Nature, 404(6773), 24–25. https://doi.org/10.1038/35003670
Marteijn, J. A., Lans, H., Vermeulen, W., & Hoeijmakers, J. H. (2014). Understanding nucleotide excision repair and its roles in cancer and ageing. Nature Reviews Molecular Cell Biology, 15(7), 465–481. https://doi.org/10.1038/nrm3822
Martínez-Reyes, I., & Chandel, N. S. (2020). Mitochondrial TCA cycle metabolites control physiology and disease. Nature Communications, 11(1), 102. https://doi.org/10.1038/s41467-019-13668-3
Maynard, S., Schurman, S. H., Harboe, C., de Souza-Pinto, N. C., & Bohr, V. A. (2009). Base excision repair of oxidative DNA damage and association with cancer and aging. Carcinogenesis, 30(1), 2–10. https://doi.org/10.1093/carcin/bgn250
Mazat, J. P., Devin, A., & Ransac, S. (2020). Modelling mitochondrial ros production by the respiratory chain. Cellular and Molecular Life Sciences, 77(3), 455–465. https://doi.org/10.1007/s00018-019-03381-1
McCord, R. A., Michishita, E., Hong, T., Berber, E., Boxer, L. D., Kusumoto, R., & Chua, K. F. (2009). Sirt6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair. Aging (albany NY), 1(1), 109–121. https://doi.org/10.18632/aging.100011
Mei, Z., Zhang, X., Yi, J., Huang, J., He, J., & Tao, Y. (2016). Sirtuins in metabolism, DNA repair and cancer. Journal of Experimental & Clinical Cancer Research, 35(1), 182. https://doi.org/10.1186/s13046-016-0461-5
Meng, Q., Zaharieva, E. K., Sasatani, M., & Kobayashi, J. (2021). Possible relationship between mitochondrial changes and oxidative stress under low dose-rate irradiation. Redox Report, 26(1), 160–169. https://doi.org/10.1080/13510002.2021.1971363
Meng, Y., Chen, C. W., Yung, M. M. H., Sun, W., Sun, J., Li, Z., & Zhu, W. (2018). Duoxa1-mediated ros production promotes cisplatin resistance by activating atr-chk1 pathway in ovarian cancer. Cancer Letters, 428, 104–116. https://doi.org/10.1016/j.canlet.2018.04.029
Miyahara, K., Takano, N., Yamada, Y., Kazama, H., Tokuhisa, M., Hino, H., & Miyazawa, K. (2021). Brca1 degradation in response to mitochondrial damage in breast cancer cells. Science and Reports, 11(1), 8735. https://doi.org/10.1038/s41598-021-87698-7
Miyamoto, S. (2011). Nuclear initiated nf-kappab signaling: Nemo and atm take center stage. Cell Research, 21(1), 116–130. https://doi.org/10.1038/cr.2010.179
Monaghan, R. M., & Whitmarsh, A. J. (2015). Mitochondrial proteins moonlighting in the nucleus. Trends in Biochemical Sciences, 40(12), 728–735. https://doi.org/10.1016/j.tibs.2015.10.003
Ran, Q., Jin, F., Xiang, Y., Xiang, L., Wang, Q., Li, F., & Li, Z. (2019). Crif1 as a potential target to improve the radiosensitivity of osteosarcoma. Proceedings of the National Academy of Sciences of the United States of America, 116(41), 20511–20516. https://doi.org/10.1073/pnas.1906578116
Rao, X., Duan, X., Mao, W., Li, X., Li, Z., Li, Q., & Yi, W. (2015). O-glcnacylation of g6pd promotes the pentose phosphate pathway and tumor growth. Nature Communications, 6, 8468. https://doi.org/10.1038/ncomms9468
Ray Chaudhuri, A., & Nussenzweig, A. (2017). The multifaceted roles of parp1 in DNA repair and chromatin remodelling. Nature Reviews Molecular Cell Biology, 18(10), 610–621. https://doi.org/10.1038/nrm.2017.53
Rose, M., Burgess, J. T., O’Byrne, K., Richard, D. J., & Bolderson, E. (2020). Parp inhibitors: Clinical relevance, mechanisms of action and tumor resistance. Frontiers in Cell and Developmental Biology, 8, 564601. https://doi.org/10.3389/fcell.2020.564601
Sack, M. N., & Finkel, T. (2012). Mitochondrial metabolism, sirtuins, and aging. Cold Spring Harbor Perspectives in Biology. https://doi.org/10.1101/cshperspect.a013102
Sang, X., Belmessabih, N., Wang, R., Stephen, P., & Lin, S. X. (2022). Crif1-cdk2 interface inhibitors enhance taxol inhibition of the lethal triple-negative breast cancer. Cancers (basel). https://doi.org/10.3390/cancers14040989
Seabright, A. P., Fine, N. H. F., Barlow, J. P., Lord, S. O., Musa, I., Gray, A., & Lai, Y. C. (2020). Ampk activation induces mitophagy and promotes mitochondrial fission while activating tbk1 in a pink1-parkin independent manner. The FASEB Journal, 34(5), 6284–6301. https://doi.org/10.1096/fj.201903051R
Shangguan, X., He, J., Ma, Z., Zhang, W., Ji, Y., Shen, K., & Xue, W. (2021). Sumoylation controls the binding of hexokinase 2 to mitochondria and protects against prostate cancer tumorigenesis. Nature Communications, 12(1), 1812. https://doi.org/10.1038/s41467-021-22163-7
Sivanand, S., Rhoades, S., Jiang, Q., Lee, J. V., Benci, J., Zhang, J., & Wellen, K. E. (2017). Nuclear acetyl-coa production by acly promotes homologous recombination. Molecular Cell, 67(2), 252-265.e256. https://doi.org/10.1016/j.molcel.2017.06.008
Sonoda, E., Hochegger, H., Saberi, A., Taniguchi, Y., & Takeda, S. (2006). Differential usage of non-homologous end-joining and homologous recombination in double strand break repair. DNA Repair, 5(9), 1021–1029. https://doi.org/10.1016/j.dnarep.2006.05.022
Spinelli, J. B., & Haigis, M. C. (2018). The multifaceted contributions of mitochondria to cellular metabolism. Nature Cell Biology, 20(7), 745–754. https://doi.org/10.1038/s41556-018-0124-1
Srinivas, U. S., Tan, B. W. Q., Vellayappan, B. A., & Jeyasekharan, A. D. (2019). Ros and the DNA damage response in cancer. Redox Biology, 25, 101084. https://doi.org/10.1016/j.redox.2018.101084
Stein, L. R., & Imai, S. (2012). The dynamic regulation of NAD metabolism in mitochondria. Trends in Endocrinology and Metabolism, 23(9), 420–428. https://doi.org/10.1016/j.tem.2012.06.005
Stiff, T., O’Driscoll, M., Rief, N., Iwabuchi, K., Lobrich, M., & Jeggo, P. A. (2004). Atm and DNA-pk function redundantly to phosphorylate h2ax after exposure to ionizing radiation. Cancer Research, 64(7), 2390–2396. https://doi.org/10.1158/0008-5472.can-03-3207
Stringer, J. M., Winship, A., Zerafa, N., Wakefield, M., & Hutt, K. (2020). Oocytes can efficiently repair DNA double-strand breaks to restore genetic integrity and protect offspring health. Proceedings of the National Academy of Sciences of the United States of America, 117(21), 11513–11522. https://doi.org/10.1073/pnas.2001124117
Sulkowski, P. L., Oeck, S., Dow, J., Economos, N. G., Mirfakhraie, L., Liu, Y., & Glazer, P. M. (2020). Oncometabolites suppress DNA repair by disrupting local chromatin signalling. Nature, 582(7813), 586–591. https://doi.org/10.1038/s41586-020-2363-0
Sullivan, K. D., Palaniappan, V. V., & Espinosa, J. M. (2015). Atm regulates cell fate choice upon p53 activation by modulating mitochondrial turnover and ros levels. Cell Cycle, 14(1), 56–63. https://doi.org/10.4161/15384101.2014.973330
Thakur, R. S., Basavaraju, S., Khanduja, J. S., Muniyappa, K., & Nagaraju, G. (2015). Mycobacterium tuberculosis recg protein but not ruvab or reca protein is efficient at remodeling the stalled replication forks: Implications for multiple mechanisms of replication restart in mycobacteria. Journal of Biological Chemistry, 290(40), 24119–24139. https://doi.org/10.1074/jbc.M115.671164
Thomas, G. E., Egan, G., Garcia-Prat, L., Botham, A., Voisin, V., Patel, P. S., & Schimmer, A. D. (2022). The metabolic enzyme hexokinase 2 localizes to the nucleus in aml and normal haematopoietic stem and progenitor cells to maintain stemness. Nature Cell Biology, 24(6), 872–884. https://doi.org/10.1038/s41556-022-00925-9
Tian, H., Gao, Z., Li, H., Zhang, B., Wang, G., Zhang, Q., & Zheng, J. (2015). DNA damage response—a double-edged sword in cancer prevention and cancer therapy. Cancer Letters, 358(1), 8–16. https://doi.org/10.1016/j.canlet.2014.12.038
Titov, D. V., Cracan, V., Goodman, R. P., Peng, J., Grabarek, Z., & Mootha, V. K. (2016). Complementation of mitochondrial electron transport chain by manipulation of the nad+/nadh ratio. Science, 352(6282), 231–235. https://doi.org/10.1126/science.aad4017
Turgeon, M. O., Perry, N. J. S., & Poulogiannis, G. (2018). DNA damage, repair, and cancer metabolism. Frontiers in Oncology, 8, 15. https://doi.org/10.3389/fonc.2018.00015
Voigt, S., Sterz, K. R., Giehler, F., Mohr, A. W., Wilson, J. B., Moosmann, A., & Kieser, A. (2020). A central role of ikk2 and tpl2 in jnk activation and viral b-cell transformation. Nature Communications, 11(1), 685. https://doi.org/10.1038/s41467-020-14502-x
Wallace, D. C., Fan, W., & Procaccio, V. (2010). Mitochondrial energetics and therapeutics. Annual Review of Pathology: Mechanisms of Disease, 5, 297–348. https://doi.org/10.1146/annurev.pathol.4.110807.092314
Wallace, S. S. (2014). Base excision repair: a critical player in many games. DNA Repair (amst), 19, 14–26. https://doi.org/10.1016/j.dnarep.2014.03.030
Wang, Q., Gao, F., May, W. S., Zhang, Y., Flagg, T., & Deng, X. (2008). Bcl2 negatively regulates DNA double-strand-break repair through a nonhomologous end-joining pathway. Molecular Cell, 29(4), 488–498. https://doi.org/10.1016/j.molcel.2007.12.029
Wang, W., Li, J., Tan, J., Wang, M., Yang, J., Zhang, Z. M., & Zhou, Q. (2021). Endonuclease g promotes autophagy by suppressing mtor signaling and activating the DNA damage response. Nature Communications, 12(1), 476. https://doi.org/10.1038/s41467-020-20780-2
Wang, Y., Xu, H., Liu, T., Huang, M., Butter, P. P., Li, C., & Fan, Y. (2018). Temporal DNA-pk activation drives genomic instability and therapy resistance in glioma stem cells. JCI Insight. https://doi.org/10.1172/jci.insight.98096
Wiederkehr, A., & Demaurex, N. (2017). Illuminating redox biology using nadh- and nadph-specific sensors. Nature Methods, 14(7), 671–672. https://doi.org/10.1038/nmeth.4336
Wiehe, R. S., Gole, B., Chatre, L., Walther, P., Calzia, E., Ricchetti, M., & Wiesmuller, L. (2018). Endonuclease g promotes mitochondrial genome cleavage and replication. Oncotarget, 9(26), 18309–18326. https://doi.org/10.18632/oncotarget.24822
Wolf, B. B., Schuler, M., Echeverri, F., & Green, D. R. (1999). Caspase-3 is the primary activator of apoptotic DNA fragmentation via DNA fragmentation factor-45/inhibitor of caspase-activated dnase inactivation. Journal of Biological Chemistry, 274(43), 30651–30656. https://doi.org/10.1074/jbc.274.43.30651
Xie, X., Zhang, Y., Wang, Z., Wang, S., Jiang, X., Cui, H., & Cao, L. (2021). Atm at the crossroads of reactive oxygen species and autophagy. International Journal of Biological Sciences, 17(12), 3080–3090. https://doi.org/10.7150/ijbs.63963
Yaku, K., Okabe, K., & Nakagawa, T. (2018). Nad metabolism: implications in aging and longevity. Ageing Research Reviews, 47, 1–17. https://doi.org/10.1016/j.arr.2018.05.006
Yan, Q., Zhu, H., Lan, L., Yi, J., & Yang, J. (2017). Cleavage of ku80 by caspase-2 promotes non-homologous end joining-mediated DNA repair. DNA Repair (amst), 60, 18–28. https://doi.org/10.1016/j.dnarep.2017.10.001
Yong, C., Stewart, G. D., & Frezza, C. (2020). Oncometabolites in renal cancer. Nature Reviews Nephrology, 16(3), 156–172. https://doi.org/10.1038/s41581-019-0210-z
Youle, R. J., & Strasser, A. (2008). The bcl-2 protein family: opposing activities that mediate cell death. Nature Reviews Molecular Cell Biology, 9(1), 47–59. https://doi.org/10.1038/nrm2308
Zandarashvili, L., Langelier, M. F., Velagapudi, U. K., Hancock, M. A., Steffen, J. D., Billur, R., & Black, B. E. (2020). Structural basis for allosteric parp-1 retention on DNA breaks. Science. https://doi.org/10.1126/science.aax6367
Zeman, M. K., & Cimprich, K. A. (2014). Causes and consequences of replication stress. Nature Cell Biology, 16(1), 2–9. https://doi.org/10.1038/ncb2897
Zhang, X. N., Cheng, Q., Chen, J., Lam, A. T., Lu, Y., Dai, Z., & Zhang, Y. (2019). A ribose-functionalized nad(+) with unexpected high activity and selectivity for protein poly-adp-ribosylation. Nature Communications, 10(1), 4196. https://doi.org/10.1038/s41467-019-12215-4
Zhu, Y., Li, M., Wang, X., Jin, H., Liu, S., Xu, J., & Chen, Q. (2012). Caspase cleavage of cytochrome c1 disrupts mitochondrial function and enhances cytochrome c release. Cell Research, 22(1), 127–141. https://doi.org/10.1038/cr.2011.82
Funding
This work was supported by the National Science Fund for Excellent Young Scholars (12122510), Anhui Provincial Key R&D Program (202104a07020006).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Zhao, X., Chen, B., Wu, L. et al. Role of mitochondria in nuclear DNA damage response. GENOME INSTAB. DIS. 3, 285–294 (2022). https://doi.org/10.1007/s42764-022-00088-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s42764-022-00088-9