Loss of p21CDKN1A impairs entry to quiescence and activates a DNA damage response in normal fibroblasts induced to quiescence

Cell Cycle

Volumn 8, Issue 1, 2009, Pages 105-114

  Perucca, Paola ^a   Cazzalini, Ornella ^a   Madine, Mark ^b   Savio, Monica ^a   Laskey, Ronal Alfred ^b   Vannini, Vanio ^a   Prosperi, Ennio ^c   Stivala, Lucia Anna ^a,b,d  

^a UNIVERSITY OF PAVIA   (Italy)

^b HUTCHISON MRC RESEARCH CENTRE   (United Kingdom)

^c CNR   (Italy)

^d Sez Patologia Generale   (Italy)

Author keywords

Checkpoints; Cyclin dependent kinase inhibitors; DNA maturation; Genome instability; p21CDKN1A; Quiescence

Indexed keywords

CYCLIN A; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE INHIBITOR 1A; CYCLIN E; MINICHROMOSOME MAINTENANCE PROTEIN 2; MYC PROTEIN; PROTEIN P21; PROTEIN P53; CELL CYCLE PROTEIN; CYCLIN DEPENDENT KINASE INHIBITOR 1B; DNA; MCM2 PROTEIN, HUMAN; NUCLEAR PROTEIN;

ARTICLE; CELL AGING; CELL CYCLE ARREST; CELL CYCLE G0 PHASE; CELL CYCLE S PHASE; CELL DIFFERENTIATION; CONTROLLED STUDY; DNA DAMAGE; DNA REPLICATION; DNA SYNTHESIS; FIBROBLAST; GENE DELETION; GENOMIC INSTABILITY; HUMAN; HUMAN CELL; PROTEIN EXPRESSION; PROTEIN FUNCTION; RNA INTERFERENCE; SIGNAL TRANSDUCTION; BIOSYNTHESIS; CELL CYCLE; CYTOLOGY; ENZYMOLOGY; METABOLISM; SERUM; UPREGULATION;

CELL CYCLE; CELL CYCLE PROTEINS; CYCLIN A; CYCLIN E; CYCLIN-DEPENDENT KINASE 2; CYCLIN-DEPENDENT KINASE INHIBITOR P21; CYCLIN-DEPENDENT KINASE INHIBITOR P27; DNA; DNA DAMAGE; DNA REPLICATION; FIBROBLASTS; HUMANS; NUCLEAR PROTEINS; PROTO-ONCOGENE PROTEINS C-MYC; SERUM; TUMOR SUPPRESSOR PROTEIN P53; UP-REGULATION;

EID: 60749090193     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.8.1.7507     Document Type: Article

References (57)

1. Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell cycle control causing specific inhibition of cyclin D/CDK4. Nature 1993; 66:704-7.
2. Morgan DO. Principles of CDK regulation. Nature 1995; 374:131-4.
3. 1-phase progression. Genes Dev 1999; 13:1501-12.
4. el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, et al. WAF1, a potential mediator of p53 tumor suppression. Cell 1993; 75: 817-25.
5. 1 cyclin-dependent kinases. Cell 1993; 75:805-16.
6. waf1/cip1. Oncogene 1999; 18:5381-92.
7. Waga S, Hannon GJ, Beach D, Stillman B. The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA. Nature 1994; 369:574-8.
8. Coqueret O. New roles for p21 and p27 cell cycle inhibitors: a function for each cell compartment? Trends Cell Biol 2003; 13:65-70.
9. waf1 binds to the myc and cdc25A promoters upon DNA damage and induces transcriptional repression. J Biol Chem 2006; 281:34742-50.
10. WAF1/Cip1: more than a break to the cell cycle? Biochim Biophys Acta 2003;1471: 43-56.
11. Avkin S, Sevilya Z, Toube L, Geacintov N, Chaney SG, Oren M, et al. p53 and p21 regulate error-prone DNA repair to yield a lower mutation load. Mol Cell 2006; 22:407-13.
12. CDKN1A protein recruitment to DNA-damage sites and interaction with proliferating cell nuclear antigen. J Cell Sci 2006; 15:1517-27.
13. CDKN1A with PCNA regulates the histone acetyltransferase activity of p300 in nucleotide excision repair. Nucleic Acids Res 2008; 36:1713-22.
14. Noda A, Ning Y, Venable SF, Pereira-Smith OM, Smith JR. Cloning of senescent cell-derived inhibitors of DNA synthesis using an expression screen. Exp Cell Res 1994; 211:90-8.
15. CIP1/WAF1 gene in normal diploid human fibroblasts. Science 1997; 277:831-4.
16. Herbig U, Sedivy JM. Regulation of growth arrest in senescence: telomere damage is not the end of the story. Mech Ageing Dev 2006; 127:16-24.
17. waf1/cip1 plays a critical role in modulating senescence through changes of DNA methylation. J Cell Biochem 2006; 98:1230-48.
18. waf1cip1 expression in the absence of p53. Oncogene 1994; 9:3397-406.
19. cip1 is required for the differentiation of oligodendrocytes independently of cell cycle withdrawal. EMBO Rep 2001; 2:27-34.
20. 0 state) in fibroblasts. J Biol Chem 1996; 271:18337-41.
21. Ladha MH, Lee KY, Upton TM, Reed MF, Ewen ME. Regulation of exit from quiescence by p27 and cyclin D1-CDK4. Mol Cell Biol 1998; 18:6605-15.
22. Sgambato A, Cittadini A, Faraglia B, Weinstein IB. Multiple functions of p27(Kip1) and its alterations in tumor cells: a review. J Cell Physiol 2000; 183:18-27.
23. Itahana K, Dimri GP, Hara E, Itahana Y, Zou Y, Desprez PY, et al. A role for p53 in maintaining and establishing the quiescence growth arrest in human cells. J Biol Chem 2002;277:18206-14.
24. Sdi1 antisense RNA. Proc Natl Acad Sci 1995; 92:4352-6.
25. Pajalunga D, Mazzola A, Salzano AM, Biferi MG, De Luca G, Crescenzi M. Critical requirement for cell cycle inhibitors in sustaining non proliferative states. J Cell Biol 2007;176:806-18.
26. cip1/waf1. Science 2000; 287:1804-8.
27. Kippin TE, Martins DJ, van der Kooy D. p21 loss compromises the relative quiescence of forebrain stem cell proliferation leading to exhaustion of their proliferation capacity. Genes Dev 2005; 19:756-67.
28. kip-1 in the molecular mechanisms of steel factor-induced proliferative synergy in vitro and of p21cip-1 in the maintenance of stem/progenitor cells in vivo. Blood 1996;88:3710-9.
29. Steinman RA, Huang J, Yaroslavskiy B, Goff JP, Ball ED, Nguyen A. Regulation of p21(WAF1) expression during normal myeloid differentiation. Blood 1998; 91:4531-42.
30. Yanagisawa K, Kosaka A, Iwahana H, Nakanishi M, Tominaga S. Opposite regulation of the expression of cyclin-dependent kinase inhibitors during contact inhibition. J Biochem 1999; 125:36-40.
31. Kip1 in intestinal epithelial cell differentiation. Am J Physiol 1999; 276:1245-58.
32. Kwon YH, Jovanovic A, Serfas MS, Kiyokawa H, Tyner AL. p21 functions to maintain quiescence of p27-deficient hepatocytes. J Biol Chem 2002; 277:41417-22.
33. Cip1 collaborate to maintain the postmitotic state of auditory hair cells, their codeletion leading to DNA damage and p53-mediated apoptosis. J Neurosci 2007; 27:1434-44.
34. Madine MA, Swietlik M, Pelizon C, Romanowski P, Mills AD, Laskey RA. The roles of the MCM, ORC and Cdc6 proteins in determining the replication competence of chromatin in quiescent cells. J Struct Biol 2000; 129:198-210.
35. Lukas C, Bartkova J, Latella L, Falck J, Mailand N, Schroeder T, et al. DNA damage-activated kinase Chk2 is independent of proliferation or differentiation yet correlates with tissue biology. Cancer Res 2001; 61:4990-3.
36. Ward IM, Chen J. Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J Biol Chem 2001; 276:47759-62.
37. McGlynn AP, Wasson G, O'Connor J, McKelvey-Martin VJ, Downs CS. The bromodeoxyuridine Comet assay: detection of maturation of recently replicated DNA in individual cells. Cancer Res 1999; 59:5912-6.
38. Ray S, Atkuri KR, Deb-Basu D, Adler AS, Chang HY, Herzenberg LA, et al. MYC can induce DNA breaks in vivo and in vitro independent of reactive oxygen species. Cancer Res 2006; 66:6598-605.
39. Dominguez-Sola D, Ying CY, Grandori C, Ruggiero L, Chen B, Li M, et al. Non-transcriptional control of DNA replication by c-Myc. Nature 2007; 448:445-51.
40. Dietrich C, Wallenfan K, Oesch F, Wieser R. Differences in the mechanisms of growth control in contact-inhibited and serum-deprived human fibroblasts. Oncogene 1997;15:2743-7.
41. Zhang X, Wharton W, Donovan M, Coppola D, Croxton R, Cress WD, et al. Density-dependent growth inhibition of fibroblasts ectopically expressing p27(kip1). Mol Biol Cell 2000; 11:2117-30.
42. Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell 1994; 78:59-66.
43. Poon RY, Toyoshima H, Hunter T. Redistribution of the CDK inhibitor p27 between different cyclin. CDK complexes in the mouse fibroblast cell cycle and in cells arrested with lovastatin or ultraviolet irradiation. Mol Biol Cell 1995; 6:1197-213.
44. Coats S, Whyte P, Fero ML, Lacy S, Chung G, Randel E, et al. A new pathway for mitogen-dependent cdk2 regulation uncovered in p27(Kip1)-deficient cells. Curr Biol 1999; 9:163-73.
45. Siegenthaler JA, Miller MW. Transforming growth factor beta1 promotes cell cycle exit through the cyclin-dependent kinase inhibitor p21 in the developing cerebral cortex. J Neurosci 2005; 25:8627-36.
46. Li JM, Brooks G. Cell cycle regulatory molecules (cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors) and the cardiovascular system; potential targets for therapy? Eur Heart J 1999; 20:406-20.
47. Coller HA, Sang L, Roberts JM. A new description of cellular quiescence. PLoS Biol 2006;4:83.
48. Chassot AA, Lossaint G, Turchi L, Meneguzzi G, Fisher D, Ponzio G, et al. Confluence-induced cell cycle exit involves pre-mitotic CDK inhibition by p27(kip1) and cyclin D1 downregulation. Cell Cycle 2008; 7:2038-46.
49. Xu Y. Induction of genetic instability by gain-of-function p53 cancer mutants. Oncogene 2008; 27:3501-7.
50. Ekholm-Reed S, Méndez J, Tedesco D, Zetterberg A, Stillman B, Reed SI. Deregulation of cyclin E in human cells interferes with prereplication complex assembly. J Cell Biol 2004;165:789-800.
51. Bartkova J, Horejsí Z, Koed K, Krämer A, Tort F, Zieger K, et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 2005; 14:864-70.
52. Araya R, Hirai I, Meyerkord CL, Wang HG. Loss of RPA1 induces Chk2 phosphorylation through a caffeine-sensitive pathway. FEBS Lett 2005; 579:157-61.
53. 2 phase. Oncogene 2008;27:896-906.
54. waf1 transcription by STAT3 proteins. J Biol Chem 2003; 278:2990-6.
55. 1/S phase transition. Cell Cycle 2003;2:596-603.
56. CDKN1A recruitment to DNA excision repair foci in the UV-induced DNA damage response. Methods Mol Biol 2004; 281:73-89.
57. Collins AR. The Comet assay for DNA damage and repair. Mol Biothecnol 2004; 26:249-61.