Tight regulation of ubiquitin-mediated DNA damage response by USP3 preserves the functional integrity of hematopoietic stem cells

Journal of Experimental Medicine

Volumn 211, Issue 9, 2014, Pages 1759-1777

  Lancini, Cesare ^a   van den Berk, Paul C M ^a   Vissers, Joseph H A ^a   Gargiulo, Gaetano ^a   Song, Ji Ying ^a   Hulsman, Danielle ^a   Serresi, Michela ^a   Tanger, Ellen ^a   Blom, Marleen ^a   Vens, Conchita ^a   van Lohuizen, Maarten ^a   Jacobs, Heinz ^a   Citterio, Elisabetta ^a  

^a NETHERLANDS CANCER INSTITUTE   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

DEUBIQUITINASE; HISTONE H2A; UB SPECIFIC PROTEASE 3; UBIQUITIN; UNCLASSIFIED DRUG;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; B LYMPHOCYTE; CELL AGING; CELL CYCLE CHECKPOINT; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL RENEWAL; CONTROLLED STUDY; DNA DAMAGE RESPONSE; DNA REPAIR; DNA STRAND BREAKAGE; EMBRYONIC STEM CELL; GENETIC REGULATION; HEMATOPOIETIC STEM CELL; HEMATOPOIETIC SYSTEM; HISTONE UBIQUITINATION; IN VITRO STUDY; IN VIVO STUDY; LYMPHOID PROGENITOR CELL; MITOTIC RECOMBINATION; MOUSE; MYELOID PROGENITOR CELL; NONHUMAN; PRIORITY JOURNAL; SISTER CHROMATID EXCHANGE;

ANIMALS; CARCINOGENESIS; CELL AGING; CELL PROLIFERATION; DNA BREAKS, DOUBLE-STRANDED; DNA DAMAGE; DNA REPAIR; FEMALE; HEMATOPOIETIC STEM CELLS; HISTONES; HOMEOSTASIS; LYMPHOPENIA; MALE; MICE; MICE, 129 STRAIN; MICE, INBRED C57BL; MICE, KNOCKOUT; UBIQUITIN-SPECIFIC PROTEASES; UBIQUITINATION;

EID: 84906552235     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20131436     Document Type: Article

References (74)

1. Alt, F.W., Y. Zhang, F.-L. Meng, C. Guo, and B. Schwer. 2013. Mechanisms of programmed DNA lesions and genomic instability in the immune system. Cell. 152:417-429. http://dx.doi.org/10.1016/j.cell.2013.01.007
2. Bohgaki, T., M. Bohgaki, R. Cardoso, S. Panier, D. Zeegers, L. Li, G.S. Stewart, O. Sanchez, M.P. Hande, D. Durocher, et al. 2011. Genomic instability, defective spermatogenesis, immunodeficiency, and cancer in a mouse model of the RIDDLE syndrome. PLoS Genet. 7:e1001381. http://dx.doi.org/10.1371/journal.pgen.1001381
3. Braig, M., S. Lee, C. Loddenkemper, C. Rudolph, A.H. Peters, B. Schlegelberger, H. Stein, B. Dörken, T. Jenuwein, and C.A. Schmitt. 2005. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature. 436:660-665. http://dx.doi.org/10.1038/nature03841
4. Christensen, J.L., and I.L. Weissman. 2001. Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells. Proc. Natl. Acad. Sci. USA. 98:14541-14546. http://dx.doi.org/10.1073/pnas.261562798
5. Cui, J., Y. Song, Y. Li, Q. Zhu, P. Tan, Y. Qin, H.Y. Wang, and R.F. Wang. 2014. USP3 inhibits type I interferon signaling by deubiquitinating RIG-I-like receptors. Cell Res. 24:400-416. http://dx.doi.org/10.1038/cr.2013.170
6. Dirac, A.M., and R. Bernards. 2003. Reversal of senescence in mouse fibroblasts through lentiviral suppression of p53. J. Biol. Chem. 278:11731-11734. http://dx.doi.org/10.1074/jbc. C300023200
7. Doil, C., N. Mailand, S. Bekker-Jensen, P. Menard, D.H. Larsen, R. Pepperkok, J. Ellenberg, S. Panier, D. Durocher, J. Bartek, et al. 2009. RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Cell. 136:435-446. http://dx.doi.org/10.1016/j.cell.2008.12.041
8. Edgar, R., M. Domrachev, and A.E. Lash. 2002. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30:207-210. http://dx.doi.org/10.1093/nar/30.1.207
9. Fenech, M., M. Kirsch-Volders, A.T. Natarajan, J. Surralles, J.W. Crott, J. Parry, H. Norppa, D.A. Eastmond, J.D. Tucker, and P. Thomas. 2011. Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis. 26:125-132. http://dx.doi.org/10.1093/mutage/geq052
10. Fradet-Turcotte, A., M.D. Canny, C. Escribano-Díaz, A. Orthwein, C.C. Leung, H. Huang, M.C. Landry, J. Kitevski-LeBlanc, S.M. Noordermeer, F. Sicheri, and D. Durocher. 2013. 53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark. Nature. 499:50-54. http://dx.doi.org/10.1038/nature12318
11. Gatti, M., S. Pinato, E. Maspero, P. Soffientini, S. Polo, and L. Penengo. 2012. A novel ubiquitin mark at the N-terminal tail of histone H2As targeted by RNF168 ubiquitin ligase. Cell Cycle. 11:2538-2544. http://dx.doi.org/10.4161/cc.20919
12. Geiger, H., G. de Haan, and M.C. Florian. 2013. The ageing haematopoietic stem cell compartment. Nat. Rev. Immunol. 13:376-389. http://dx.doi.org/10.1038/nri3433
13. Ginjala, V., K. Nacerddine, A. Kulkarni, J. Oza, S.J. Hill, M. Yao, E. Citterio, M. van Lohuizen, and S. Ganesan. 2011. BMI1 is recruited to DNA breaks and contributes to DNA damage-induced H2A ubiquitination and repair. Mol. Cell. Biol. 31:1972-1982. http://dx.doi.org/10.1128/MCB.00981-10
14. Goldknopf, I.L., M.F. French, R. Musso, and H. Busch. 1977. Presence of protein A24 in rat liver nucleosomes. Proc. Natl. Acad. Sci. USA. 74:5492-5495. http://dx.doi.org/10.1073/pnas.74.12.5492
15. Gudjonsson, T., M. Altmeyer, V. Savic, L. Toledo, C. Dinant, M. Grøfte, J. Bartkova, M. Poulsen, Y. Oka, S. Bekker-Jensen, et al. 2012. TRIP12 and UBR5 suppress spreading of chromatin ubiquitylation at damaged chromosomes. Cell. 150:697-709. http://dx.doi.org/10.1016/j.cell.2012.06.039
16. Halaby, M.J., A. Hakem, L. Li, S. El Ghamrasni, S. Venkatesan, P.M. Hande, O. Sanchez, and R. Hakem. 2013. Synergistic interaction of Rnf8 and p53 in the protection against genomic instability and tumorigenesis. PLoS Genet. 9:e1003259. http://dx.doi.org/10.1371/journal.pgen.1003259
17. Hoeijmakers, J.H.J. 2009. DNA damage, aging, and cancer. N. Engl. J. Med. 361:1475-1485. http://dx.doi.org/10.1056/NEJMra0804615
18. Huen, M.S., R. Grant, I. Manke, K. Minn, X. Yu, M.B. Yaffe, and J. Chen. 2007. RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly. Cell. 131:901-914. http://dx.doi.org/10.1016/j.cell.2007.09.041
19. Ismail, I.H., C. Andrin, D. McDonald, and M.J. Hendzel. 2010. BMI1-mediated histone ubiquitylation promotes DNA double-strand break repair. J. Cell Biol. 191:45-60. http://dx.doi.org/10.1083/jcb.201003034
20. Ito, K., A. Hirao, F. Arai, S. Matsuoka, K. Takubo, I. Hamaguchi, K. Nomiyama, K. Hosokawa, K. Sakurada, N. Nakagata, et al. 2004. Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells. Nature. 431:997-1002. http://dx.doi.org/10.1038/nature02989
21. Jackson, S.P., and J. Bartek. 2009. The DNA-damage response in human biology and disease. Nature. 461:1071-1078. http://dx.doi.org/10.1038/nature08467
22. Jackson, S.P., and D. Durocher. 2013. Regulation of DNA damage responses by ubiquitin and SUMO. Mol. Cell. 49:795-807. http://dx.doi.org/10.1016/j.molcel.2013.01.017
23. Jonkers, J., R. Meuwissen, H. van der Gulden, H. Peterse, M. van der Valk, and A. Berns. 2001. Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat. Genet. 29:418-425. http://dx.doi.org/10.1038/ng747
24. + common lymphoid progenitors possess equivalent differentiation potential for the B and T lineages. Blood. 111:5562-5570. http://dx.doi.org/10.1182/blood-2007-11-126219
25. Kiel, M.J., S. He, R. Ashkenazi, S.N. Gentry, M. Teta, J.A. Kushner, T.L. Jackson, and S.J. Morrison. 2007a. Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature. 449:238-242. http://dx.doi.org/10.1038/nature06115
26. Kiel, M.J., G.L. Radice, and S.J. Morrison. 2007b. Lack of evidence that hematopoietic stem cells depend on N-cadherin-mediated adhesion to osteoblasts for their maintenance. Cell Stem Cell. 1:204-217. http://dx.doi.org/10.1016/j.stem.2007.06.001
27. Kolas, N.K., J.R. Chapman, S. Nakada, J. Ylanko, R. Chahwan, F.D. Sweeney, S. Panier, M. Mendez, J. Wildenhain, T.M. Thomson, et al. 2007. Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science. 318:1637-1640. http://dx.doi.org/10.1126/science.1150034
28. Komander, D., M.J. Clague, and S. Urbé. 2009. Breaking the chains: structure and function of the deubiquitinases. Nat. Rev. Mol. Cell Biol. 10:550-563. http://dx.doi.org/10.1038/nrm2731
29. Kuilman, T., C. Michaloglou, W.J. Mooi, and D.S. Peeper. 2010. The essence of senescence. Genes Dev. 24:2463-2479. http://dx.doi.org/10.1101/gad.1971610
30. Li, L., M.J. Halaby, A. Hakem, R. Cardoso, S. El Ghamrasni, S. Harding, N. Chan, R. Bristow, O. Sanchez, D. Durocher, and R. Hakem. 2010. Rnf8 deficiency impairs class switch recombination, spermatogenesis, and genomic integrity and predisposes for cancer. J. Exp. Med. 207:983-997. http://dx.doi.org/10.1084/jem.20092437
31. Lukas, J., C. Lukas, and J. Bartek. 2011. More than just a focus: The chromatin response to DNA damage and its role in genome integrity maintenance. Nat. Cell Biol. 13:1161-1169. http://dx.doi.org/10.1038/ncb2344
32. Mailand, N., S. Bekker-Jensen, H. Faustrup, F. Melander, J. Bartek, C. Lukas, and J. Lukas. 2007. RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell. 131:887-900. http://dx.doi.org/10.1016/j.cell.2007.09.040
33. Mattiroli, F., J.H.A. Vissers, W.J. van Dijk, P. Ikpa, E. Citterio, W. Vermeulen, J.A. Marteijn, and T.K. Sixma. 2012. RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling. Cell. 150:1182-1195. http://dx.doi.org/10.1016/j.cell.2012.08.005
34. Milyavsky, M., O.I. Gan, M. Trottier, M. Komosa, O. Tabach, F. Notta, E. Lechman, K.G. Hermans, K. Eppert, Z. Konovalova, 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. 7:186-197. http://dx.doi.org/10.1016/j.stem.2010.05.016
35. Mohrin, M., E. Bourke, D. Alexander, M.R. Warr, K. Barry-Holson, M.M. Le Beau, C.G. Morrison, and E. Passegué. 2010. Hematopoietic stem cell quiescence promotes error-prone DNA repair and mutagenesis. Cell Stem Cell. 7:174-185. http://dx.doi.org/10.1016/j.stem.2010.06.014
36. Morrison, S.J., and A.C. Spradling. 2008. Stem cells and niches: mechanisms that promote stem cell maintenance throughout life. Cell. 132:598-611. http://dx.doi.org/10.1016/j.cell.2008.01.038
37. Morrison, S.J., N. Uchida, and I.L. Weissman. 1995. The biology of hematopoietic stem cells. Annu. Rev. Cell Dev. Biol. 11:35-71. http://dx.doi.org/10.1146/annurev.cb.11.110195.000343
38. Morrison, S.J., A.M. Wandycz, K. Akashi, A. Globerson, and I.L. Weissman. 1996. The aging of hematopoietic stem cells. Nat. Med. 2:1011-1016. http://dx.doi.org/10.1038/nm0996-1011
39. Mosbech, A., C. Lukas, S. Bekker-Jensen, and N. Mailand. 2013. The deubiquitylating enzyme USP44 counteracts the DNA double-strand break response mediated by the RNF8 and RNF168 ubiquitin ligases. J. Biol. Chem. 288:16579-16587. http://dx.doi.org/10.1074/jbc. M113.459917
40. Moyal, L., Y. Lerenthal, M. Gana-Weisz, G. Mass, S. So, S.-Y. Wang, B. Eppink, Y.M. Chung, G. Shalev, E. Shema, et al. 2011. Requirement of ATM-dependent monoubiquitylation of histone H2B for timely repair of DNA double-strand breaks. Mol. Cell. 41:529-542. http://dx.doi.org/10.1016/j.molcel.2011.02.015
41. Nakamura, K., A. Kato, J. Kobayashi, H. Yanagihara, S. Sakamoto, D.V. Oliveira, M. Shimada, H. Tauchi, H. Suzuki, S. Tashiro, et al. 2011. Regulation of homologous recombination by RNF20-dependent H2B ubiquitination. Mol. Cell. 41:515-528. http://dx.doi.org/10.1016/j.molcel.2011.02.002
42. Narita, M., S. Nuñez, E. Heard, M. Narita, A.W. Lin, S.A. Hearn, D.L. Spector, G.J. Hannon, and S.W. Lowe. 2003. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell. 113:703-716. http://dx.doi.org/10.1016/S0092-8674(03)00401-X
43. Neijenhuis, S., M. Verwijs-Janssen, L.J. van den Broek, A.C. Begg, and C. Vens. 2010. Targeted radiosensitization of cells expressing truncated DNA polymerase beta. Cancer Res. 70:8706-8714. http://dx.doi.org/10.1158/0008-5472.CAN-09-3901
44. Nicassio, F., N. Corrado, J.H. Vissers, L.B. Areces, S. Bergink, J.A. Marteijn, B. Geverts, A.B. Houtsmuller, W. Vermeulen, P.P. Di Fiore, and E. Citterio. 2007. Human USP3 is a chromatin modifier required for S phase progression and genome stability. Curr. Biol. 17:1972-1977. http://dx.doi.org/10.1016/j.cub.2007.10.034
45. Niedernhofer, L.J. 2008. DNA repair is crucial for maintaining hematopoietic stem cell function. DNA Repair (Amst.). 7:523-529. http://dx.doi.org/10.1016/j.dnarep.2007.11.012
46. Nijnik, A., L. Woodbine, C. Marchetti, S. Dawson, T. Lambe, C. Liu, N.P. Rodrigues, T.L. Crockford, E. Cabuy, A. Vindigni, et al. 2007. DNA repair is limiting for haematopoietic stem cells during ageing. Nature. 447:686-690. http://dx.doi.org/10.1038/nature05875
47. Osawa, M., K. Hanada, H. Hamada, and H. Nakauchi. 1996. Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science. 273:242-245. http://dx.doi.org/10.1126/science.273.5272.242
48. Pang, W.W., E.A. Price, D. Sahoo, I. Beerman, W.J. Maloney, D.J. Rossi, S.L. Schrier, and I.L. Weissman. 2011. Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age. Proc. Natl. Acad. Sci. USA. 108:20012-20017. http://dx.doi.org/10.1073/pnas.1116110108
49. Panier, S., and D. Durocher. 2013. Push back to respond better: regulatory inhibition of the DNA double-strand break response. Nat. Rev. Mol. Cell Biol. 14:661-672. http://dx.doi.org/10.1038/nrm3659
50. Pinato, S., C. Scandiuzzi, N. Arnaudo, E. Citterio, G. Gaudino, and L. Penengo. 2009. RNF168, a new RING finger, MIU-containing protein that modifies chromatin by ubiquitination of histones H2A and H2AX. BMC Mol. Biol. 10:55. http://dx.doi.org/10.1186/1471-2199-10-55
51. Polo, S.E., and S.P. Jackson. 2011. Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications. Genes Dev. 25:409-433. http://dx.doi.org/10.1101/gad.2021311
52. Purton, L.E., S. Dworkin, G.H. Olsen, C.R. Walkley, S.A. Fabb, S.J. Collins, and P. Chambon. 2006. RARγ is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation. J. Exp. Med. 203:1283-1293. http://dx.doi.org/10.1084/jem.20052105
53. Reimann, M., S. Lee, C. Loddenkemper, J.R. Dörr, V. Tabor, P. Aichele, H. Stein, B. Dörken, T. Jenuwein, and C.A. Schmitt. 2010. Tumor stroma-derived TGF-β limits myc-driven lymphomagenesis via Suv39h1-dependent senescence. Cancer Cell. 17:262-272. http://dx.doi.org/10.1016/j.ccr.2009.12.043
54. Robanus-Maandag, E., M. Dekker, M. van der Valk, M.L. Carrozza, J.C. Jeanny, J.H. Dannenberg, A. Berns, and H. te Riele. 1998. p107 is a suppressor of retinoblastoma development in pRb-deficient mice. Genes Dev. 12:1599-1609. http://dx.doi.org/10.1101/gad.12.11.1599
55. Rodrigues, N.P., A.S. Boyd, C. Fugazza, G.E. May, Y. Guo, A.J. Tipping, D.T. Scadden, P. Vyas, and T. Enver. 2008. GATA-2 regulates granulocyte-macrophage progenitor cell function. Blood. 112:4862-4873. http://dx.doi.org/10.1182/blood-2008-01-136564
56. Rodríguez, C.I., F. Buchholz, J. Galloway, R. Sequerra, J. Kasper, R. Ayala, A.F. Stewart, and S.M. Dymecki. 2000. High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat. Genet. 25:139-140. http://dx.doi.org/10.1038/75973
57. Rogakou, E.P., D.R. Pilch, A.H. Orr, V.S. Ivanova, and W.M. Bonner. 1998. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J. Biol. Chem. 273:5858-5868. http://dx.doi.org/10.1074/jbc.273.10.5858
58. Rossi, D.J., D. Bryder, J. Seita, A. Nussenzweig, J. Hoeijmakers, and I.L. Weissman. 2007. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature. 447:725-729. http://dx.doi.org/10.1038/nature05862
59. Rossi, D.J., C.H. Jamieson, and I.L. Weissman. 2008. Stems cells and the pathways to aging and cancer. Cell. 132:681-696. http://dx.doi.org/10.1016/j.cell.2008.01.036
60. Rübe, C.E., A. Fricke, T.A. Widmann, T. Fürst, H. Madry, M. Pfreundschuh, and C. Rübe. 2011. Accumulation of DNA damage in hematopoietic stem and progenitor cells during human aging. PLoS ONE. 6:e17487. http://dx.doi.org/10.1371/journal.pone.0017487
61. Shanbhag, N.M., I.U. Rafalska-Metcalf, C. Balane-Bolivar, S.M. Janicki, and R.A. Greenberg. 2010. ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks. Cell. 141:970-981. http://dx.doi.org/10.1016/j.cell.2010.04.038
62. Sharma, N., Q. Zhu, G. Wani, J. He, Q.E. Wang, and A.A. Wani. 2014. USP3 counteracts RNF168 via deubiquitinating H2A and γH2AX at lysine 13 and 15. Cell Cycle. 13:106-114. http://dx.doi.org/10.4161/cc.26814
63. Simon, J.A., and R.E. Kingston. 2013. Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put. Mol. Cell. 49:808-824. http://dx.doi.org/10.1016/j.molcel.2013.02.013
64. Sonoda, E., M.S. Sasaki, C. Morrison, Y. Yamaguchi-Iwai, M. Takata, and S. Takeda. 1999. Sister chromatid exchanges are mediated by homologous recombination in vertebrate cells. Mol. Cell. Biol. 19:5166-5169. PubMed
65. Sperka, T., J. Wang, and K.L. Rudolph. 2012. DNA damage checkpoints in stem cells, ageing and cancer. Nat. Rev. Mol. Cell Biol. 13:579-590. http://dx.doi.org/10.1038/nrm3420
66. Stewart, G.S., S. Panier, K. Townsend, A.K. Al-Hakim, N.K. Kolas, E.S. Miller, S. Nakada, J. Ylanko, S. Olivarius, M. Mendez, et al. 2009. The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage. Cell. 136:420-434. http://dx.doi.org/10.1016/j.cell.2008.12.042
67. Sulli, G., R. Di Micco, and F. d'Adda di Fagagna. 2012. Crosstalk between chromatin state and DNA damage response in cellular senescence and cancer. Nat. Rev. Cancer. 12:709-720. http://dx.doi.org/10.1038/nrc3344
68. van der Weyden, L., D.J. Adams, L.W. Harris, D. Tannahill, M.J. Arends, and A. Bradley. 2005. Null and conditional semaphorin 3B alleles using a flexible puroΔtk loxP/FRT vector. Genesis. 41:171-178. http://dx.doi.org/10.1002/gene.20111
69. van Os, R.P., B. Dethmers-Ausema, and G. de Haan. 2008. In vitro assays for cobblestone area-forming cells, LTC-IC, and CFU-C. Methods Mol. Biol. 430:143-157. http://dx.doi.org/10.1007/978-1-59745-182-6_10
70. Vissers, J.H., M. van Lohuizen, and E. Citterio. 2012. The emerging role of Polycomb repressors in the response to DNA damage. J. Cell Sci. 125:3939-3948. http://dx.doi.org/10.1242/jcs.107375
71. Wang, B., S. Matsuoka, B.A. Ballif, D. Zhang, A. Smogorzewska, S.P. Gygi, and S.J. Elledge. 2007. Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science. 316:1194-1198. http://dx.doi.org/10.1126/science.1139476
72. Wang, J., Q. Sun, Y. Morita, H. Jiang, A. Gross, A. Lechel, K. Hildner, L.M. Guachalla, A. Gompf, D. Hartmann, et al. 2012. A differentiation checkpoint limits hematopoietic stem cell self-renewal in response to DNA damage. Cell. 148:1001-1014. http://dx.doi.org/10.1016/j.cell.2012.01.040
73. Ward, I.M., K. Minn, J. van Deursen, and J. Chen. 2003. p53 Binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice. Mol. Cell. Biol. 23:2556-2563. http://dx.doi.org/10.1128/MCB.23.7.2556-2563.2003
74. Yeung, J., and C.W. So. 2009. Identification and characterization of hematopoietic stem and progenitor cell populations in mouse bone marrow by flow cytometry. Methods Mol. Biol. 538:301-315. http://dx.doi.org/10.1007/978-1-59745-418-6_15