DNA damage in stem cells activates p21, inhibits p53, and induces symmetric self-renewing divisions

Proceedings of the National Academy of Sciences of the United States of America

Volumn 110, Issue 10, 2013, Pages 3931-3936

  Insinga, Alessandra ^a   Cicalese, Angelo ^a   Faretta, Mario ^a   Gallo, Barbara ^a   Albano, Luisa ^a   Ronzoni, Simona ^a   Furia, Laura ^a   Viale, Andrea ^a   Pelicci, Pier Giuseppe ^a,b  

^a EUROPEAN INSTITUTE OF ONCOLOGY   (Italy)

^b UNIVERSITY OF MILAN   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; PROTEIN P21; PROTEIN P53;

ANIMAL EXPERIMENT; ANIMAL TISSUE; APOPTOSIS; ARTICLE; BREAST CELL; CELL CYCLE; CELL DIVISION; CELL RENEWAL; CONTROLLED STUDY; DNA DAMAGE; HEMATOPOIESIS; INHIBITION KINETICS; IRRADIATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; STEM CELL; UPREGULATION; X RAY;

ADULT STEM CELLS; ANIMALS; APOPTOSIS; CELL CYCLE CHECKPOINTS; CELL DIVISION; CYCLIN-DEPENDENT KINASE INHIBITOR P21; DNA DAMAGE; DNA REPAIR; FEMALE; HEMATOPOIETIC STEM CELLS; MAMMARY GLANDS, ANIMAL; MICE; MICE, 129 STRAIN; MICE, INBRED C57BL; MICE, KNOCKOUT; TUMOR SUPPRESSOR PROTEIN P53; UP-REGULATION;

EID: 84874611142     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1213394110     Document Type: Article

References (28)

1. Blanpain C, Mohrin M, Sotiropoulou PA, Passegué E (2011) DNA-damage response in tissue-specific and cancer stem cells. Cell Stem Cell 8(1):16-29.
2. Lane AA, Scadden DT (2010) Stem cells and DNA damage: Persist or perish? Cell 142(3):360-362.
3. Seita J, Rossi DJ, Weissman IL (2010) Differential DNA damage response in stem and progenitor cells. Cell Stem Cell 7(2):145-147.
4. Xu H, et al. (2010) Rad21-cohesin haploinsufficiency impedes DNA repair and enhances gastrointestinal radiosensitivity in mice. PLoS ONE 5(8):e12112.
5. Sotiropoulou PA, et al. (2010) Bcl-2 and accelerated DNA repair mediates resistance of hair follicle bulge stem cells to DNA-damage-induced cell death. Nat Cell Biol 12(6):572-582.
6. Nijnik A, et al. (2007) DNA repair is limiting for haematopoietic stem cells during ageing. Nature 447(7145):686-690.
7. Rübe CE, et al. (2011) Accumulation of DNA damage in hematopoietic stem and progenitor cells during human aging. PLoS ONE 6(3):e17487.
8. Rossi DJ, et al. (2007) Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature 447(7145):725-729.
9. Sedelnikova OA, et al. (2008) Delayed kinetics of DNA double-strand break processing in normal and pathological aging. Aging Cell 7(1):89-100.
10. Meek DW (2009) Tumour suppression by p53: A role for the DNA damage response? Nat Rev Cancer 9(10):714-723.
11. Levine AJ, Oren M (2009) The first 30 years of p53: Growing ever more complex. Nat Rev Cancer 9(10):749-758.
12. Mohrin M, et al. (2010) Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis. Cell Stem Cell 7(2):174-185.
13. Hendry JH, Cai WB, Roberts SA, Potten CS (1997) p53 deficiency sensitizes clonogenic cells to irradiation in the large but not the small intestine. Radiat Res 148(3):254-259.
14. Merritt AJ, et al. (1994) The role of p53 in spontaneous and radiation-induced apoptosis in the gastrointestinal tract of normal and p53-deficient mice. Cancer Res 54(3): 614-617.
15. Qiu W, et al. (2008) PUMA regulates intestinal progenitor cell radiosensitivity and gastrointestinal syndrome. Cell Stem Cell 2(6):576-583.
16. Cheng T, et al. (2000) Hematopoietic stem cell quiescence maintained by p21cip1/waf1. Science 287(5459):1804-1808.
17. van Os R, et al. (2007) A limited role for p21Cip1/Waf1 in maintaining normal hematopoietic stem cell functioning. Stem Cells 25(4):836-843.
18. Rossi DJ, et al. (2007) Hematopoietic stem cell quiescence attenuates DNA damage response and permits DNA damage accumulation during aging. Cell Cycle 6(19):2371-2376.
19. Cicalese A, et al. (2009) The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells. Cell 138(6):1083-1095.
20. Ishikawa K, Ishii H, Saito T (2006) DNA damage-dependent cell cycle checkpoints and genomic stability. DNA Cell Biol 25(7):406-411.
21. Weissman IL, Shizuru JA (2008) The origins of the identification and isolation of hematopoietic stem cells, and their capability to induce donor-specific transplantation tolerance and treat autoimmune diseases. Blood 112(9):3543-3553.
22. Sharpless NE, DePinho RA (2007) How stem cells age and why this makes us grow old. Nat Rev Mol Cell Biol 8(9):703-713.
23. Milyavsky M, et al. (2010) A distinctive DNA damage response in human hematopoietic stem cells reveals an apoptosis-independent role for p53 in self-renewal. Cell Stem Cell 7(2):186-197.
24. Orkin SH, Zon LI (2008) Hematopoiesis: An evolving paradigm for stem cell biology. Cell 132(4):631-644.
25. Aliouat-Denis CM, et al. (2005) p53-independent regulation of p21Waf1/Cip1 expression and senescence by Chk2. Mol Cancer Res 3(11):627-634.
26. Cazzalini O, Scovassi AI, Savio M, Stivala LA, Prosperi E (2010) Multiple roles of the cell cycle inhibitor p21(CDKN1A) in the DNA damage response. Mutat Res 704(1-3): 12-20.
27. Davis RL, Turner DL (2001) Vertebrate hairy and Enhancer of split related proteins: Transcriptional repressors regulating cellular differentiation and embryonic patterning. Oncogene 20(58):8342-8357.
28. Viale A, et al. (2009) Cell-cycle restriction limits DNA damage and maintains self-renewal of leukaemia stem cells. Nature 457(7225):51-56.