Persistent repair intermediates induce senescence
Jazyk angličtina Země Anglie, Velká Británie Médium electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
NKI 2014-6787
KWF Kankerbestrijding (Dutch Cancer Society) - International
NKI 2014-6787
KWF Kankerbestrijding (Dutch Cancer Society) - International
16-19437S
Grantová Agentura České Republiky (Grant Agency of the Czech Republic) - International
PubMed
30254262
PubMed Central
PMC6156224
DOI
10.1038/s41467-018-06308-9
PII: 10.1038/s41467-018-06308-9
Knihovny.cz E-zdroje
- MeSH
- ATM protein genetika metabolismus MeSH
- buněčné linie MeSH
- časosběrné zobrazování metody MeSH
- cyklin B1 genetika metabolismus MeSH
- fluorescenční mikroskopie MeSH
- HEK293 buňky MeSH
- inhibitor p21 cyklin-dependentní kinasy genetika metabolismus MeSH
- kontrolní body fáze G2 buněčného cyklu genetika MeSH
- lidé MeSH
- oprava DNA genetika MeSH
- poškození DNA * MeSH
- signální transdukce genetika MeSH
- stárnutí buněk genetika MeSH
- zelené fluorescenční proteiny genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ATM protein MeSH
- ATR protein, human MeSH Prohlížeč
- CCNB1 protein, human MeSH Prohlížeč
- cyklin B1 MeSH
- inhibitor p21 cyklin-dependentní kinasy MeSH
- zelené fluorescenční proteiny MeSH
Double-stranded DNA breaks activate a DNA damage checkpoint in G2 phase to trigger a cell cycle arrest, which can be reversed to allow for recovery. However, damaged G2 cells can also permanently exit the cell cycle, going into senescence or apoptosis, raising the question how an individual cell decides whether to recover or withdraw from the cell cycle. Here we find that the decision to withdraw from the cell cycle in G2 is critically dependent on the progression of DNA repair. We show that delayed processing of double strand breaks through HR-mediated repair results in high levels of resected DNA and enhanced ATR-dependent signalling, allowing p21 to rise to levels at which it drives cell cycle exit. These data imply that cells have the capacity to discriminate breaks that can be repaired from breaks that are difficult to repair at a time when repair is still ongoing.
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Shaltiel IA, Krenning L, Bruinsma W, Medema RH. The same, only different - DNA damage checkpoints and their reversal throughout the cell cycle. J. Cell Sci. 2015;128:607–620. doi: 10.1242/jcs.163766. PubMed DOI
Ciccia A, Elledge SJ. The DNA damage response: making it safe to play with knives. Mol. Cell. 2010;40:179–204. doi: 10.1016/j.molcel.2010.09.019. PubMed DOI PMC
Khanna KK, Jackson SP. DNA double-strand breaks: signaling, repair and the cancer connection. Nat. Genet. 2001;27:247–254. doi: 10.1038/85798. PubMed DOI
Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature. 2009;461:1071–1078. doi: 10.1038/nature08467. PubMed DOI PMC
Blackford AN, Jackson SP. ATM, ATR, and DNA-PK: the Trinity at the Heart of the DNA Damage Response. Mol. Cell. 2017;66:801–817. doi: 10.1016/j.molcel.2017.05.015. PubMed DOI
Maréchal A, Zou L. DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb. Perspect. Biol. 2013;5:a012716–a012716. doi: 10.1101/cshperspect.a012716. PubMed DOI PMC
Uziel T, et al. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J. 2003;22:5612–5621. doi: 10.1093/emboj/cdg541. PubMed DOI PMC
Brown EJ, Baltimore D. Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev. 2003;17:615–628. doi: 10.1101/gad.1067403. PubMed DOI PMC
Cortez D, Guntuku S, Qin J, Elledge SJ. ATR and ATRIP: partners in checkpoint signaling. Science. 2001;294:1713–1716. doi: 10.1126/science.1065521. PubMed DOI
Zou L, Elledge SJ. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science. 2003;300:1542–1548. doi: 10.1126/science.1083430. PubMed DOI
Baumann P, Benson FE, West SC. Human Rad51 protein promotes ATP-dependent homologous pairing and strand transfer reactions in vitro. Cell. 1996;87:757–766. doi: 10.1016/S0092-8674(00)81394-X. PubMed DOI
Jensen RB, Carreira A, Kowalczykowski SC. Purified human BRCA2 stimulates RAD51-mediated recombination. Nature. 2010;467:678–683. doi: 10.1038/nature09399. PubMed DOI PMC
Krenning L, Feringa FM, Shaltiel IA, van den Berg J, Medema RH. Transient activation of p53 in G2 phase is sufficient to induce senescence. Mol. Cell. 2014;55:59–72. doi: 10.1016/j.molcel.2014.05.007. PubMed DOI
Müllers E, Silva Cascales H, Jaiswal H, Saurin AT, Lindqvist A. Nuclear translocation of Cyclin B1 marks the restriction point for terminal cell cycle exit in G2 phase. Cell Cycle. 2014;13:2733–2743. doi: 10.4161/15384101.2015.945831. PubMed DOI PMC
Johmura Y, et al. Necessary and sufficient role for a mitosis skip in senescence induction. Mol. Cell. 2014;55:73–84. doi: 10.1016/j.molcel.2014.05.003. PubMed DOI
Feringa FM, et al. Hypersensitivity to DNA damage in antephase as a safeguard for genome stability. Nat. Commun. 2016;7:12618. doi: 10.1038/ncomms12618. PubMed DOI PMC
Toledo LI, Murga M, Gutierrez-Martinez P, Soria R, Fernandez-Capetillo O. ATR signaling can drive cells into senescence in the absence of DNA breaks. Genes Dev. 2008;22:297–302. doi: 10.1101/gad.452308. PubMed DOI PMC
Jazayeri A, et al. ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat. Cell Biol. 2006;8:37–45. doi: 10.1038/ncb1337. PubMed DOI
Myers JS, Cortez D. Rapid activation of ATR by ionizing radiation requires ATM and Mre11. J. Biol. Chem. 2006;281:9346–9350. doi: 10.1074/jbc.M513265200. PubMed DOI PMC
Shiotani B, Zou L. Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks. Mol. Cell. 2009;33:547–558. doi: 10.1016/j.molcel.2009.01.024. PubMed DOI PMC
Tomimatsu N, Mukherjee B, Burma S. Distinct roles of ATR and DNA-PKcs in triggering DNA damage responses in ATM-deficient cells. EMBO Rep. 2009;10:629–635. doi: 10.1038/embor.2009.60. PubMed DOI PMC
Xue L, et al. The complexity of DNA double strand break is a crucial factor for activating ATR signaling pathway for G2/M checkpoint regulation regardless of ATM function. DNA Repair (Amst.) 2015;25:72–83. doi: 10.1016/j.dnarep.2014.11.004. PubMed DOI
Lindqvist A, et al. Wip1 confers G2 checkpoint recovery competence by counteracting p53-dependent transcriptional repression. EMBO J. 2009;28:3196–3206. doi: 10.1038/emboj.2009.246. PubMed DOI PMC
Lu X, Nannenga B, Donehower LA. PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Genes Dev. 2005;19:1162–1174. doi: 10.1101/gad.1291305. PubMed DOI PMC
Shreeram S, et al. Wip1 phosphatase modulates ATM-dependent signaling pathways. Mol. Cell. 2006;23:757–764. doi: 10.1016/j.molcel.2006.07.010. PubMed DOI
Yamaguchi H, Durell SR, Chatterjee DK, Anderson CW, Appella E. The Wip1 phosphatase PPM1D dephosphorylates SQ/TQ motifs in checkpoint substrates phosphorylated by PI3K-like kinases. Biochemistry. 2007;46:12594–12603. doi: 10.1021/bi701096s. PubMed DOI
Kleiblova P, et al. Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint. J. Cell Biol. 2013;201:511–521. doi: 10.1083/jcb.201210031. PubMed DOI PMC
Yata K, et al. Plk1 and CK2 act in concert to regulate Rad51 during DNA double strand break repair. Mol. Cell. 2012;45:371–383. doi: 10.1016/j.molcel.2011.12.028. PubMed DOI PMC
Smits VA, et al. Polo-like kinase-1 is a target of the DNA damage checkpoint. Nat. Cell Biol. 2000;2:672–676. doi: 10.1038/35023629. PubMed DOI
Bruinsma W, et al. Inhibition of Polo-like kinase 1 during the DNA damage response is mediated through loss of Aurora A recruitment by Bora. Oncogene. 2016;36:1840–1848. doi: 10.1038/onc.2016.347. PubMed DOI PMC
Wang L, Guo Q, Fisher LA, Liu D, Peng A. Regulation of polo-like kinase 1 by DNA damage and PP2A/B55α. Cell Cycle. 2015;14:157–166. doi: 10.4161/15384101.2014.986392. PubMed DOI PMC
Tomimatsu N, et al. Phosphorylation of EXO1 by CDKs 1 and 2 regulates DNA end resection and repair pathway choice. Nat. Commun. 2014;5:3561. doi: 10.1038/ncomms4561. PubMed DOI PMC
Deans AJ, et al. Cyclin-dependent kinase 2 functions in normal DNA repair and is a therapeutic target in BRCA1-deficient cancers. Cancer Res. 2006;66:8219–8226. doi: 10.1158/0008-5472.CAN-05-3945. PubMed DOI
Ferretti, L. P., Lafranchi, L. & Sartori, A. A. Controlling DNA-end resection: a new task for CDKs. Front. Genet.4, 99 (2013). PubMed PMC
Huertas P, Cortés-Ledesma F, Sartori AA, Aguilera A, Jackson SP. CDK targets Sae2 to control DNA-end resection and homologous recombination. Nature. 2008;455:689–692. doi: 10.1038/nature07215. PubMed DOI PMC
Ira G, et al. DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1. Nature. 2004;431:1011–1017. doi: 10.1038/nature02964. PubMed DOI PMC
Myers JS, Zhao R, Xu X, Ham AJL, Cortez D. Cyclin-dependent kinase 2 dependent phosphorylation of ATRIP regulates the G2-M checkpoint response to DNA damage. Cancer Res. 2007;67:6685–6690. doi: 10.1158/0008-5472.CAN-07-0495. PubMed DOI PMC
Müllers E, Silva Cascales H, Burdova K, Macurek L, Lindqvist A. Residual Cdk1/2 activity after DNA damage promotes senescence. Aging Cell. 2017;16:575–584. doi: 10.1111/acel.12588. PubMed DOI PMC
Wyman C, Ristic D, Kanaar R. Homologous recombination-mediated double-strand break repair. DNA Repair (Amst.) 2004;3:827–833. doi: 10.1016/j.dnarep.2004.03.037. PubMed DOI
Villemure JF, Abaji C, Cousineau I, Belmaaza A. MSH2-deficient human cells exhibit a defect in the accurate termination of homology-directed repair of DNA double-strand breaks. Cancer Res. 2003;63:3334–3339. PubMed
Abbas T, et al. PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. Genes Dev. 2008;22:2496–2506. doi: 10.1101/gad.1676108. PubMed DOI PMC
Kim Y, Starostina NG, Kipreos ET. The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to control replication licensing. Genes Dev. 2008;22:2507–2519. doi: 10.1101/gad.1703708. PubMed DOI PMC
Nishitani H, et al. CDK inhibitor p21 is degraded by a proliferating cell nuclear antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV irradiation. J. Biol. Chem. 2008;283:29045–29052. doi: 10.1074/jbc.M806045200. PubMed DOI PMC
Hindriksen S, et al. Baculoviral delivery of CRISPR/Cas9 facilitates efficient genome editing in human cells. PLoS One. 2017;12:e0179514. doi: 10.1371/journal.pone.0179514. PubMed DOI PMC