7,956
Views
158
CrossRef citations to date
0
Altmetric
PERSPECTIVE

Senescence from G2 arrest, revisited

&
Pages 297-304 | Received 26 Aug 2014, Accepted 15 Dec 2014, Published online: 06 Feb 2015

References

  • Kuilman T, Michaloglou C, Mooi WJ Peeper DS. The essence of senescence. Genes Dev 2010; 24:2463-79; PMID:21078816; http://dx.doi.org/10.1101/gad.1971610
  • Salama R, Sadaie M, Hoare M Narita M. Cellular senescence and its effector programs. Genes Dev 2014; 28:99-114; PMID:24449267; http://dx.doi.org/10.1101/gad.235184.113
  • Burkhart DL Sage J. Cellular mechanisms of tumour suppression by the retinoblastoma gene. Nat Rev Cancer 2008; 8:671-82; PMID:18650841; http://dx.doi.org/10.1038/nrc2399
  • Polager S Ginsberg D. p53 and E2f: partners in life and death. Nat Rev Cancer 2009; 9:738-48; PMID:19776743; http://dx.doi.org/10.1038/nrc2718
  • Lavin MF. Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Biol 2008; 9:759-69; PMID:18813293; http://dx.doi.org/10.1038/nrm2514
  • Demidenko ZN, Korotchkina LG, Gudkov AV Blagosklonny MV. Paradoxical suppression of cellular senescence by p53. Proc Natl Acad Sci U S A 2010; 107:9660-4; PMID:20457898; http://dx.doi.org/10.1073/pnas.1002298107
  • Kolesnichenko M, Hong L, Liao R, Vogt PK Sun P. Attenuation of TORC1 signaling delays replicative and oncogenic RAS-induced senescence. Cell Cycle 2012; 11:2391-401; PMID:22627671; http://dx.doi.org/10.4161/cc.20683
  • Dulic V. Senescence regulation by mTOR. Methods Mol Biol 2013; 965:15-35; PMID:23296649; http://dx.doi.org/10.1007/978-1-62703-239-1_2
  • Hasty P, Sharp ZD, Curiel TJ Campisi J. mTORC1 and p53: clash of the gods? Cell Cycle 2013; 12:20-5; PMID:23255104; http://dx.doi.org/10.4161/cc.22912
  • Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, Vassiliou LV, Kolettas E, Niforou K, Zoumpourlis VC, et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 2006; 444:633-7; PMID:17136093; http://dx.doi.org/10.1038/nature05268
  • Adams PD. Healing and hurting: molecular mechanisms, functions, and pathologies of cellular senescence. Mol Cell 2009; 36:2-14; PMID:19818705; http://dx.doi.org/10.1016/j.molcel.2009.09.021
  • Rodier F Campisi J. Four faces of cellular senescence. J Cell Biol 2011; 192:547-56; PMID:21321098; http://dx.doi.org/10.1083/jcb.201009094
  • Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, Guldberg P, Sehested M, Nesland JM, Lukas C, et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 2005; 434:864-70; PMID:15829956; http://dx.doi.org/10.1038/nature03482
  • Gorgoulis VG, Vassiliou LV, Karakaidos P, Zacharatos P, Kotsinas A, Liloglou T, Venere M, Ditullio RA, Jr., Kastrinakis NG, Levy B, et al. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 2005; 434:907-13; PMID:15829965; http://dx.doi.org/10.1038/nature03485
  • Collado M Serrano M. Senescence in tumours: evidence from mice and humans. Nat Rev Cancer 2010; 10:51-7; PMID:20029423; http://dx.doi.org/10.1038/nrc2772
  • Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, Kirkland JL van Deursen JM. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 2011; 479:232-6; PMID:22048312; http://dx.doi.org/10.1038/nature10600
  • Kang TW, Yevsa T, Woller N, Hoenicke L, Wuestefeld T, Dauch D, Hohmeyer A, Gereke M, Rudalska R, Potapova A, et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 2011; 479:547-551; PMID:22080947; http://dx.doi.org/10.1038/nature10599
  • Krtolica A, Parrinello S, Lockett S, Desprez PY Campisi J. Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc Natl Acad Sci U S A 2001; 98:12072-7; PMID:11593017; http://dx.doi.org/10.1073/pnas.211053698
  • Coppe JP, Patil CK, Rodier F, Sun Y, Munoz DP, Goldstein J, Nelson PS, Desprez PY Campisi J. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 2008; 6:2853-68; PMID:19053174; http://dx.doi.org/10.1371/journal.pbio.0060301
  • Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, Cordon-Cardo C Lowe SW. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007; 445:656-60; PMID:17251933; http://dx.doi.org/10.1038/nature05529
  • Munoz-Espin D, Canamero M, Maraver A, Gomez-Lopez G, Contreras J, Murillo-Cuesta S, Rodriguez-Baeza A, Varela-Nieto I, Ruberte J, Collado M et al. Programmed cell senescence during mammalian embryonic development. Cell 2013; 155:1104-18; PMID:24238962; http://dx.doi.org/10.1016/j.cell.2013.10.019
  • Storer M, Mas A, Robert-Moreno A, Pecoraro M, Ortells MC, Di Giacomo V, Yosef R, Pilpel N, Krizhanovsky V, Sharpe J et al. Senescence is a developmental mechanism that contributes to embryonic growth and patterning. Cell 2013; 155:1119-30; PMID:24238961; http://dx.doi.org/10.1016/j.cell.2013.10.041
  • Krizhanovsky V, Yon M, Dickins RA, Hearn S, Simon J, Miething C, Yee H, Zender L Lowe SW. Senescence of activated stellate cells limits liver fibrosis. Cell 2008; 134:657-67; PMID:18724938; http://dx.doi.org/10.1016/j.cell.2008.06.049
  • Jun JI Lau LF. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nat Cell Biol 2010; 12:676-85; PMID:20526329; http://dx.doi.org/10.1038/ncb2070
  • Stein GH Dulic V. Origins of G1 arrest in senescent human fibroblasts. Bioessays 1995; 17:537-43; PMID:7575495; http://dx.doi.org/10.1002/bies.950170610
  • Smith JR Pereira-Smith OM. Replicative senescence: implications for in vivo aging and tumor suppression. Science 1996; 273:63-7; PMID:8658197; http://dx.doi.org/10.1126/science.273.5271.63
  • Dulic V, Drullinger LF, Lees E, Reed SI Stein GH. Altered regulation of G1 cyclins in senescent human diploid fibroblasts: accumulation of inactive cyclin E-Cdk2 and cyclin D1-Cdk2 complexes. Proc Natl Acad Sci U S A 1993; 90:11034-8; PMID:8248208; http://dx.doi.org/10.1073/pnas.90.23.11034
  • Stein GH, Drullinger LF, Soulard A Dulic V. Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. Mol Cell Biol 1999; 19:2109-17; PMID:10022898
  • Harbour JW, Luo RX, Dei Santi A, Postigo AA Dean DC. Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell 1999; 98:859-69; PMID:10499802; http://dx.doi.org/10.1016/S0092-8674(00)81519-6
  • Sherr CJ Roberts JM. Living with or without cyclins and cyclin-dependent kinases. Genes Dev 2004; 18:2699-711; PMID:15545627; http://dx.doi.org/10.1101/gad.1256504
  • Hwang HC Clurman BE. Cyclin E in normal and neoplastic cell cycles. Oncogene 2005; 24:2776-86; PMID:15838514; http://dx.doi.org/10.1038/sj.onc.1208613
  • Dulic V, Kaufmann WK, Wilson SJ, Tlsty TD, Lees E, Harper JW, Elledge SJ Reed SI. p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell 1994; 76:1013-23; PMID:8137420; http://dx.doi.org/10.1016/0092-8674(94)90379-4
  • Waldman T, Kinzler KW Vogelstein B. p21 is necessary for the p53-mediated G1 arrest in human cancer cells. Cancer Res 1995; 55:5187-90; PMID:7585571
  • d'Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T, Saretzki G, Carter NP Jackson SP. A DNA damage checkpoint response in telomere-initiated senescence. Nature 2003; 426:194-8; PMID:14608368; http://dx.doi.org/10.1038/nature02118
  • Gire V. Dysfunctional telomeres at senescence signal cell cycle arrest via Chk2. Cell Cycle 2004; 3:1217-20; PMID:15467458; http://dx.doi.org/10.4161/cc.3.10.1167
  • d'Adda di Fagagna F. Living on a break: cellular senescence as a DNA-damage response. Nat Rev Cancer 2008; 8:512-22; PMID:18574463; http://dx.doi.org/10.1038/nrc2440
  • Di Micco R, Fumagalli M, Cicalese A, Piccinin S, Gasparini P, Luise C, Schurra C, Garre M, Nuciforo PG, Bensimon A, et al. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 2006; 444:638-42; PMID:17136094; http://dx.doi.org/10.1038/nature05327
  • Mallette FA, Gaumont-Leclerc MF Ferbeyre G. The DNA damage signaling pathway is a critical mediator of oncogene-induced senescence. Genes Dev 2007; 21:43-8; PMID:17210786; http://dx.doi.org/10.1101/gad.1487307
  • Chicas A, Wang X, Zhang C, McCurrach M, Zhao Z, Mert O, Dickins RA, Narita M, Zhang M Lowe SW. Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence. Cancer Cell 2010; 17:376-87; PMID:20385362; http://dx.doi.org/10.1016/j.ccr.2010.01.023
  • Stein GH, Beeson M Gordon L. Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts. Science 1990; 249:666-9; PMID:2166342; http://dx.doi.org/10.1126/science.2166342
  • Stein GH, Drullinger LF, Robetorye RS, Pereira-Smith OM Smith JR. Senescent cells fail to express cdc2, cycA, and cycB in response to mitogen stimulation. Proc Natl Acad Sci U S A 1991; 88:11012-6; PMID:1722313; http://dx.doi.org/10.1073/pnas.88.24.11012
  • Alcorta DA, Xiong Y, Phelps D, Hannon G, Beach D Barrett JC. Involvement of the cyclin-dependent kinase inhibitor p16 (INK4a) in replicative senescence of normal human fibroblasts. Proc Natl Acad Sci U S A 1996; 93:13742-7; PMID:8943005; http://dx.doi.org/10.1073/pnas.93.24.13742
  • Serrano M, Lin AW, McCurrach ME, Beach D Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 1997; 88:593-602; PMID:9054499; http://dx.doi.org/10.1016/S0092-8674(00)81902-9
  • Sandhu C, Peehl DM Slingerland J. p16INK4A mediates cyclin dependent kinase 4 and 6 inhibition in senescent prostatic epithelial cells. Cancer Res 2000; 60:2616-22; PMID:10825132
  • Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O and et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 1995; 92:9363-7; PMID:7568133; http://dx.doi.org/10.1073/pnas.92.20.9363
  • Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L Sharpless NE. Ink4a/Arf expression is a biomarker of aging. J Clin Invest 2004; 114:1299-307; PMID:15520862; http://dx.doi.org/10.1172/JCI22475
  • Burd CE, Sorrentino JA, Clark KS, Darr DB, Krishnamurthy J, Deal AM, Bardeesy N, Castrillon DH, Beach DH Sharpless NE. Monitoring tumorigenesis and senescence in vivo with a p16(INK4a)-luciferase model. Cell 2013; 152:340-51; PMID:23332765; http://dx.doi.org/10.1016/j.cell.2012.12.010
  • Wei W, Herbig U, Wei S, Dutriaux A Sedivy JM. Loss of retinoblastoma but not p16 function allows bypass of replicative senescence in human fibroblasts. EMBO Rep 2003; 4:1061-6; PMID:14566323; http://dx.doi.org/10.1038/sj.embor.7400001
  • Beausejour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P Campisi J. Reversal of human cellular senescence: roles of the p53 and p16 pathways. Embo J 2003; 22:4212-22; PMID:12912919; http://dx.doi.org/10.1093/emboj/cdg417
  • Herbig U, Jobling WA, Chen BP, Chen DJ Sedivy JM. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol Cell 2004; 14:501-13; PMID:15149599; http://dx.doi.org/10.1016/S1097-2765(04)00256-4
  • Gil J Peters G. Regulation of the INK4b-ARF-INK4a tumour suppressor locus: all for one or one for all. Nat Rev Mol Cell Biol 2006; 7:667-77; PMID:16921403; http://dx.doi.org/10.1038/nrm1987
  • Witkiewicz AK, Knudsen KE, Dicker AP Knudsen ES. The meaning of p16(ink4a) expression in tumors: functional significance, clinical associations and future developments. Cell Cycle 2011; 10:2497-503; PMID:21775818; http://dx.doi.org/10.4161/cc.10.15.16776
  • Waldman T, Lengauer C, Kinzler KW Vogelstein B. Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21. Nature 1996; 381:713-6; PMID:8649519; http://dx.doi.org/10.1038/381713a0
  • Dulic V, Stein GH, Far DF Reed SI. Nuclear accumulation of p21Cip1 at the onset of mitosis: a role at the G2/M-phase transition. Mol Cell Biol 1998; 18:546-57; PMID:9418901
  • Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW Vogelstein B. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 1998; 282:1497-501; PMID:9822382; http://dx.doi.org/10.1126/science.282.5393.1497
  • Abraham RT. Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev 2001; 15:2177-96; PMID:11544175; http://dx.doi.org/10.1101/gad.914401
  • Levedakou EN, Kaufmann WK, Alcorta DA, Galloway DA Paules RS. p21CIP1 is not required for the early G2 checkpoint response to ionizing radiation. Cancer Res 1995; 55:2500-2; PMID:7780956
  • Smits VA, Klompmaker R, Vallenius T, Rijksen G, Makela TP Medema RH. p21 inhibits Thr161 phosphorylation of Cdc2 to enforce the G2 DNA damage checkpoint. J Biol Chem 2000; 275:30638-43; PMID:10913154; http://dx.doi.org/10.1074/jbc.M005437200
  • Baus F, Gire V, Fisher D, Piette J Dulic V. Permanent cell cycle exit in G2 phase after DNA damage in normal human fibroblasts. Embo J 2003; 22:3992-4002; PMID:12881433; http://dx.doi.org/10.1093/emboj/cdg387
  • Flatt PM, Tang LJ, Scatena CD, Szak ST Pietenpol JA. p53 regulation of G(2) checkpoint is retinoblastoma protein dependent. Mol Cell Biol 2000; 20:4210-4223; PMID:10825186; http://dx.doi.org/10.1128/MCB.20.12.4210-4223.2000
  • Passalaris TM, Benanti JA, Gewin L, Kiyono T Galloway DA. The G(2) checkpoint is maintained by redundant pathways. Mol Cell Biol 1999; 19:5872-5881; PMID:10454534
  • Crawford DF Piwnica-Worms H. The G(2) DNA damage checkpoint delays expression of genes encoding mitotic regulators. J Biol Chem 2001; 276:37166-77; PMID:11483598; http://dx.doi.org/10.1074/jbc.M103414200
  • Ren B, Cam H, Takahashi Y, Volkert T, Terragni J, Young RA Dynlacht BD. E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints. Genes Dev 2002; 16:245-256; PMID:11799067; http://dx.doi.org/10.1101/gad.949802
  • Jackson MW, Agarwal MK, Yang J, Bruss P, Uchiumi T, Agarwal ML, Stark GR Taylor WR. p130/p107/p105Rb-dependent transcriptional repression during DNA-damage-induced cell-cycle exit at G2. J Cell Sci 2005; 118:1821-32; PMID:15827088; http://dx.doi.org/10.1242/jcs.02307
  • Lanni JS Jacks T. Characterization of the p53-dependent postmitotic checkpoint following spindle disruption. Mol Cell Biol 1998; 18:1055-64; PMID:9448003
  • Stewart ZA, Leach SD Pietenpol JA. p21(Waf1/Cip1) inhibition of cyclin E/Cdk2 activity prevents endoreduplication after mitotic spindle disruption. Mol Cell Biol 1999; 19:205-15; PMID:9858545
  • Andreassen PR, Lacroix FB, Lohez OD Margolis RL. Neither p21(WAF1) Nor 14-3-3sigma Prevents G(2) Progression to Mitotic Catastrophe in Human Colon Carcinoma Cells after DNA Damage, But p21(WAF1) Induces Stable G(1) Arrest in Resulting Tetraploid Cells. Cancer Res 2001; 61:7660-8; PMID:11606409
  • Davoli T de Lange T. The causes and consequences of polyploidy in normal development and cancer. Annu Rev Cell Dev Biol 2011; 27:585-610; PMID:21801013; http://dx.doi.org/10.1146/annurev-cellbio-092910-154234
  • Charrier-Savournin FB, Chateau MT, Gire V, Sedivy J, Piette J Dulic V. p21-Mediated nuclear retention of cyclin B1-Cdk1 in response to genotoxic stress. Mol Biol Cell 2004; 15:3965-76; PMID:15181148; http://dx.doi.org/10.1091/mbc.E03-12-0871
  • Chan TA, Hermeking H, Lengauer C, Kinzler KW Vogelstein B. 14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage ; see comments. Nature 1999; 401:616-620; PMID:10524633; http://dx.doi.org/10.1038/44188
  • Winters ZE, Ongkeko WM, Harris AL Norbury CJ. p53 regulates Cdc2 independently of inhibitory phosphorylation to reinforce radiation-induced G2 arrest in human cells. Oncogene 1998; 17:673-84; PMID:9715268; http://dx.doi.org/10.1038/sj.onc.1201991
  • Lossaint G, Besnard E, Fisher D, Piette J Dulic V. Chk1 is dispensable for G2 arrest in response to sustained DNA damage when the ATM/p53/p21 pathway is functional. Oncogene 2011; 30:4261-74; PMID:21532626; http://dx.doi.org/10.1038/onc.2011.135
  • Foijer F, Wolthuis RM, Doodeman V, Medema RH te Riele H. Mitogen requirement for cell cycle progression in the absence of pocket protein activity. Cancer Cell 2005; 8:455-66; PMID:16338659; http://dx.doi.org/10.1016/j.ccr.2005.10.021
  • Lee J, Kim JA, Barbier V, Fotedar A Fotedar R. DNA damage triggers p21WAF1-dependent Emi1 down-regulation that maintains G2 arrest. Mol Biol Cell 2009; 20:1891-902; PMID:19211842; http://dx.doi.org/10.1091/mbc.E08-08-0818
  • Gillis LD, Leidal AM, Hill R Lee PW. p21Cip1/WAF1 mediates cyclin B1 degradation in response to DNA damage. Cell Cycle 2009; 8:253-6; PMID:19158493; http://dx.doi.org/10.4161/cc.8.2.7550
  • Wiebusch L Hagemeier C. p53- and p21-dependent premature APC/C-Cdh1 activation in G2 is part of the long-term response to genotoxic stress. Oncogene 2010; 29:3477-89; PMID:20383190; http://dx.doi.org/10.1038/onc.2010.99
  • Bassermann F, Frescas D, Guardavaccaro D, Busino L, Peschiaroli A Pagano M. The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint. Cell 2008; 134:256-67; PMID:18662541; http://dx.doi.org/10.1016/j.cell.2008.05.043
  • Lobrich M Jeggo PA. The impact of a negligent G2/M checkpoint on genomic instability and cancer induction. Nat Rev Cancer 2007; 7:861-9; PMID:17943134; http://dx.doi.org/10.1038/nrc2248
  • Mao Z, Ke Z, Gorbunova V Seluanov A. Replicatively senescent cells are arrested in G1 and G2 phases. Aging (Albany NY) 2012; 4:431-5; PMID:22745179
  • Leontieva OV, Lenzo F, Demidenko ZN Blagosklonny MV. Hyper-mitogenic drive coexists with mitotic incompetence in senescent cells. Cell Cycle 2012; 11:4642-9; PMID:23187803; http://dx.doi.org/10.4161/cc.22937
  • Jullien L, Mestre M, Roux P Gire V. Eroded human telomeres are more prone to remain uncapped and to trigger a G2 checkpoint response. Nucleic Acids Res 2013; 41:900-11; PMID:23193277
  • Verdun RE, Crabbe L, Haggblom C Karlseder J. Functional human telomeres are recognized as DNA damage in G2 of the cell cycle. Mol Cell 2005; 20:551-61; PMID:16307919; http://dx.doi.org/10.1016/j.molcel.2005.09.024
  • Cesare AJ, Hayashi MT, Crabbe L Karlseder J. The telomere deprotection response is functionally distinct from the genomic DNA damage response. Mol Cell 2013; 51:141-55; PMID:23850488; http://dx.doi.org/10.1016/j.molcel.2013.06.006
  • Ahn J, Urist M Prives C. Questioning the role of checkpoint kinase 2 in the p53 DNA damage response. J Biol Chem 2003; 278:20480-9; PMID:12654916; http://dx.doi.org/10.1074/jbc.M213185200
  • Jallepalli PV, Lengauer C, Vogelstein B Bunz F. The Chk2 tumor suppressor is not required for p53 responses in human cancer cells. J Biol Chem 2003; 278:20475-9; PMID:12654917; http://dx.doi.org/10.1074/jbc.M213159200
  • Gong Y de Lange T. A Shld1-controlled POT1a provides support for repression of ATR signaling at telomeres through RPA exclusion. Mol Cell 2010; 40:377-87; PMID:21070964; http://dx.doi.org/10.1016/j.molcel.2010.10.016
  • Gire V, Roux P, Wynford-Thomas D, Brondello JM Dulic V. DNA damage checkpoint kinase Chk2 triggers replicative senescence. Embo J 2004; 23:2554-63; PMID:15192702; http://dx.doi.org/10.1038/sj.emboj.7600259
  • Davoli T, Denchi EL de Lange T. Persistent telomere damage induces bypass of mitosis and tetraploidy. Cell 2010; 141:81-93; PMID:20371347; http://dx.doi.org/10.1016/j.cell.2010.01.031
  • Toettcher JE, Loewer A, Ostheimer GJ, Yaffe MB, Tidor B Lahav G. Distinct mechanisms act in concert to mediate cell cycle arrest. Proc Natl Acad Sci U S A 2009; 106:785-90; PMID:19139404; http://dx.doi.org/10.1073/pnas.0806196106
  • Ye C, Zhang X, Wan J, Chang L, Hu W, Bing Z, Zhang S, Li J, He J, Wang J, et al. Radiation-induced cellular senescence results from a slippage of long-term G2 arrested cells into G1 phase. Cell Cycle 2013; 12:1424-32; PMID:23574719; http://dx.doi.org/10.4161/cc.24528
  • Sakaue-Sawano A, Kurokawa H, Morimura T, Hanyu A, Hama H, Osawa H, Kashiwagi S, Fukami K, Miyata T, Miyoshi H, Imamura T, Ogawa M, Masai H Miyawaki A. Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell 2008; 132:487-98; PMID:18267078; http://dx.doi.org/10.1016/j.cell.2007.12.033
  • Davoli T de Lange T. Telomere-driven tetraploidization occurs in human cells undergoing crisis and promotes transformation of mouse cells. Cancer Cell 2012; 21:765-76; PMID:22698402; http://dx.doi.org/10.1016/j.ccr.2012.03.044
  • Johmura Y, Shimada M, Misaki T, Naiki-Ito A, Miyoshi H, Motoyama N, Ohtani N, Hara E, Nakamura M, Morita A, et al. Necessary and Sufficient Role for a Mitosis Skip in Senescence Induction. Mol Cell 2014; 55:73-84; PMID:24910096
  • Michaloglou C, Vredeveld LC, Soengas MS, Denoyelle C, Kuilman T, van der Horst CM, Majoor DM, Shay JW, Mooi WJ Peeper DS. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 2005; 436:720-4; PMID:16079850; http://dx.doi.org/10.1038/nature03890
  • 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; PMID:24910099
  • Müllers E, Cascales HS, 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; PMID:25486360; http://dx.doi.org/10.4161/15384101.2015.945831
  • Kleiblova P, Shaltiel IA, Benada J, Sevcik J, Pechackova S, Pohlreich P, Voest EE, Dundr P, Bartek J, Kleibl Z, et al. Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint. J Cell Biol 2013; 201:511-21; PMID:23649806; http://dx.doi.org/10.1083/jcb.201210031
  • Abbas T Dutta A. p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 2009; 9:400-14; PMID:19440234; http://dx.doi.org/10.1038/nrc2657
  • Chassot AA, Lossaint G, Turchi L, Meneguzzi G, Fisher D, Ponzio G Dulic V. Confluence-induced cell cycle exit involves pre-mitotic CDK inhibition by p27(Kip1) and cyclin D1 downregulation. Cell Cycle 2008; 7:2038-46; PMID:18604165; http://dx.doi.org/10.4161/cc.7.13.6233
  • Spencer SL, Cappell SD, Tsai FC, Overton KW, Wang CL Meyer T. The proliferation-quiescence decision is controlled by a bifurcation in CDK2 activity at mitotic exit. Cell 2013; 155:369-83; PMID:24075009; http://dx.doi.org/10.1016/j.cell.2013.08.062

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.