Mechanism of CRL4 cdt2, a PCNA-dependent E3 ubiquitin ligase

Genes and Development

Volumn 25, Issue 15, 2011, Pages 1568-1582

  Havens, Courtney G ^a   Walter, Johannes C ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Cdt2; Cna; Crl4; Cul4; Ddb1; Pip degron

Indexed keywords

CRL4 CDT2 PROTEIN; CYCLIN DEPENDENT KINASE INHIBITOR 1; CYCLIN DEPENDENT KINASE INHIBITOR 1B; CYCLIN DEPENDENT KINASE INHIBITOR 1C; DNA DIRECTED DNA POLYMERASE ETA; PROTEIN; REPLICATION LICENSING FACTOR CDT1; SET8 PROTEIN; SPD1 PROTEIN; TRANSCRIPTION FACTOR E2F; UBIQUITIN PROTEIN LIGASE; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG;

ARTICLE; CELL CYCLE S PHASE; CELL FUNCTION; DNA REPAIR; DNA REPLICATION; HOMEOSTASIS; HUMAN; MOLECULAR DOCKING; MOLECULAR MECHANICS; MOLECULAR RECOGNITION; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN FUNCTION; PROTEIN PROCESSING; UBIQUITINATION;

ANIMALS; CELL CYCLE PROTEINS; DNA REPAIR; DNA REPLICATION; HUMANS; NUCLEAR PROTEINS; PROLIFERATING CELL NUCLEAR ANTIGEN; PROTEIN PROCESSING, POST-TRANSLATIONAL; UBIQUITIN-PROTEIN LIGASES; UBIQUITINATION; XENOPUS PROTEINS;

EUKARYOTA;

EID: 80051525031     PISSN: 08909369     EISSN: 15495477     Source Type: Journal    
DOI: 10.1101/gad.2068611     Document Type: Article

References (141)

1. Abbas T, Dutta A. 2011. CRL4Cdt2: master coordinator of cell cycle progression and genome stability. Cell Cycle 10: 241-249.
2. Abbas T, Sivaprasad U, Terai K, Amador V, Pagano M, Dutta A. 2008. PCNA-dependent regulation of p21 ubiquitylation and degradation via the CRL4Cdt2 ubiquitin ligase complex. Genes Dev 22: 2496-2506.
3. Abbas T, Shibata E, Park J, Jha S, Karnani N, Dutta A. 2010. CRL4(Cdt2) regulates cell proliferation and histone gene expression by targeting PR-Set7/Set8 for degradation. Mol Cell 40: 9-21.
4. Adimoolam S, Lin CX, Ford JM. 2001. The p53-regulated cyclindependent kinase inhibitor, p21 (cip1, waf1, sdi1), is not required for global genomic and transcription-coupled nucleotide excision repair of UV-induced DNA photoproducts. J Biol Chem 276: 25813-25822.
5. Amador V, Ge S, Santamaria PG, Guardavaccaro D, Pagano M. 2007. APC/C(Cdc20) controls the ubiquitin-mediated degradation of p21 in prometaphase. Mol Cell 27: 462-473.
6. Angers S, Li T, Yi X, MacGoss MJ, Moon RT, Zheng N. 2006. Molecular architecture and assembly of the Ddb1-Cul4A ubiquitin ligase machinery. Nature 443: 590-593.
7. Ardley HC, Robinson PA. 2005. E3 ubiquitin ligases. Essays Biochem 41: 15-30.
8. Arias EE, Walter JC. 2005. Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts. Genes Dev 19: 114-126
9. Arias EE, Walter JC. 2006. PCNA functions as a molecular platform to trigger Cdt1 destruction and prevent re-replication. Nat Cell Biol 8: 84-90.
10. Arias EE, Walter JC. 2007. Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells. Genes Dev 21: 427-518.
11. Asano M, Nevins JR, Wharton RP. 1996. Ectopic E2F expression induces S phase and apoptosis in Drosophila imaginal discs. Genes Dev 10: 1422-1432.
12. Bates S, Ryan KM, Phillips AC, Vousden KH. 1998. Cell cycle arrest and DNA endoreduplication following p21Waf1/Cip1 expression. Oncogene 17: 1691-1703.
13. Behrends C, Harper JW. 2011. Constructing and decoding unconventional ubiquitin chains. Nat Struct Mol Biol 18: 520-528.
14. Bendjennat M, Boulaire J, Jascur T, Brickner H, Barbier V, Sarasin A, Fotedar A, Fotedar R. 2003. UV irradiation triggers ubiquitin-dependent degradation of p21(WAF1) to promote DNA repair. Cell 114: 599-610.
15. Bornstein G, Bloom J, Sitry-Shevah D, Nakayama K, Pagano M, Hershko A. 2003. Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase. J Biol Chem 278: 25752-25757.
16. Braun S, Garcia JF, Rowley M, Rougemaille M, Shankar S, Madhani HD. 2011. The Cul4-Ddb1(Cdt)(2) ubiquitin ligase inhibits invasion of a boundary-associated antisilencing factor into heterochromatin. Cell 144: 41-54.
17. Cayrol C, Knibiehler M, Ducommun B. 1998. p21 binding to PCNA causes G1 and G2 cell cycle arrest in p53-deficient cells. Oncogene 16: 311-320.
18. Cazzalini O, Perucca P, Riva F, Stivala LA, Bianchi L, Vannini V, Ducommun B, Prosperi E. 2003. p21CDKN1A does not interfere with loading of PCNA at DNA replication sites, but inhibits subsequent binding of DNA polymerase d at the G1/S phase transition. Cell Cycle 2: 596-603.
19. Centore RC, Havens CG, Manning AL, Li JM, Flynn RL, Tse A, Jin J, Dyson NJ, Walter JC, Zou L. 2010. CRL4(Cdt2)-mediated destruction of the histone methyltransferase Set8 prevents premature chromatin compaction in S phase. Mol Cell 40: 22-33.
20. Chen J, Jackson PK, Kirschner MW, Dutta A. 1995. Separate domains of p21 involved in the inhibition of Cdk kinase and PCNA. Nature 374: 386-388.
21. Choe KP, Przybysz AJ, Strange K. 2009. The WD40 repeat protein WDR-23 functions with the CUL4/DDB1 ubiquitin ligase to regulate nuclear abundance and activity of SKN-1 in Caenorhabditis elegans. Mol Cell Biol 29: 2704-2715.
22. Chuang LC, Yew PR. 2005. PCNA recruits CDK inhibitor Xic1 to DNA and couples its proteolysis to DNA polymerase switching. J Biol Chem 280: 35299-35309.
23. Chuang LC, Zhu XN, Herrera CR, Tseng HM, Pfleger CM, Block K, Yew PR. 2005. The C-terminal domain of the Xenopus cyclin-dependent kinase inhibitor, p27Xic1, is both necessary and sufficient for phosphorylation-independent proteolysis. J Biol Chem 280: 34290-35285.
24. Cooper MP, Balajee AS, Bohr VA. 1999. The C-terminal domain of p21 inhibits nucleotide excision repair in vitro and in vivo. Mol Biol Cell 10: 2119-2129.
25. Deshaies RJ, Joazeiro CA. 2009. RING domain E3 ubiquitin ligases. Annu Rev Biochem 78: 399-434.
26. Deshaies RJ, Emberley ED, Saha A. 2010. Control of cullin-ring ubiquitin ligase activity by nedd8. Subcell Biochem 54: 41-56.
27. Dimova DK, Dyson NJ. 2005. The E2F transcriptional network: old acquaintances with new faces. Oncogene 24: 2810-2826.
28. Duda DM, Borg LA, Scott DC, Hunt HW, Hammel M, Schulman BA. 2008. Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. Cell 134: 995-1006.
29. Fridman Y, Palgi N, Dovrat D, Ben-Aroya S, Hieter P, Aharoni A. 2010. Subtle alterations in PCNA-partner interactions severely impair DNA replication and repair. PLoS Biol 8: doi: 10.1371/journal.pbio.1000507
30. Gao D, Inuzuka H, Tseng A, Chin RY, Toker A, Wei W. 2009. Phosphorylation by Akt1 promotes cytoplasmic localization of Skp2 and impairs APCCdh1-mediated Skp2 destruction. Nat Cell Biol 11: 397-408.
31. Guarino E, Shepherd ME, Salguero I, Hua H, Deegan RS, Kearsey SE. 2011. Cdt1 proteolysis is promoted by dual PIP degrons and is modulated by PCNA ubiquitylation. Nucleic Acids Res doi: 10.1093/nar/gkr222
32. Gulbis JM, Kelman Z, Hurwitz J, O'Donnell M, Kuriyan J. 1996. Structure of the C-terminal region of p21(WAF1/CIP1) complexed with human PCNA. Cell 87: 297-306.
33. Hao B, Oehlmann S, Sowa ME, Harper JW, Pavletich NP. 2007. Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases. Mol Cell 26: 131-143.
34. Havens CG, Walter JC. 2009. Docking of a specialized PIP Box onto chromatin-bound PCNA creates a degron for the ubiquitin ligase CRL4Cdt2. Mol Cell 35: 93-104.
35. He YJ, McCall CM, Hu J, Zeng Y, Xiong Y. 2006. DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases. Genes Dev 20: 2949-2954.
36. Higa LA, Zhang H. 2007. Stealing the spotlight: CUL4-DDB1 ubiquitin ligase docks WD40-repeat proteins to destroy. Cell Div 2: 5.
37. Higa LA, Mihaylov IS, Banks DP, Zheng J, Zhang H. 2003. Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes constitutes a new checkpoint. Nat Cell Biol 5: 1008-1015.
38. Higa LA, Banks D, Wu M, Kobayashi R, Sun H, Zhang H. 2006a. L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage. Cell Cycle 5: 1675-1680.
39. Higa LA, Wu M, Ye T, Kobayashi R, Sun H, Zhang H. 2006b. CUL4-DDB1 ubiquitin ligase interacts with multiple WD40- repeat proteins and regulates histone methylation. Nat Cell Biol 8: 1277-1283.
40. Hoege C, Pfander B, Moldovan GL, Pyrowolakis G, Jentsch S. 2002. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419: 135-141
41. Hofmann JF, Beach D. 1994. cdt1 is an essential target of the Cdc10/Sct1 transcription factor: requirement for DNA replication and inhibition of mitosis. EMBO J 13: 425-434.
42. Holmberg C, Fleck O, Hansen HA, Liu C, Slaaby R, Carr AM, Nielsen O. 2005. Ddb1 controls genome stability and meiosis in fission yeast. Genes Dev 19: 853-862.
43. Hon WC, Wilson MI, Harlos K, Claridge TD, Schofield CJ, Pugh CW, Maxwell PH, Ratcliffe PJ, Stuart DI, Jones EY. 2002. Structural basis for the recognition of hydroxyproline in HIF- 1a by pVHL. Nature 417: 975-978.
44. Hook SS, Lin JJ, Dutta A. 2007. Mechanisms to control rereplication and implications for cancer. Curr Opin Cell Biol 19: 663-671.
45. Houston SI, McManus KJ, Adams MM, Sims JK, Carpenter PB, Hendzel MJ, Rice JC. 2008. Catalytic function of the PR-Set7 histone H4 lysine 20 monomethyltransferase is essential for mitotic entry and genomic stability. J Biol Chem 283: 19478-19488.
46. Hu J, Xiong Y. 2006. An evolutionarily conserved function of proliferating cell nuclear antigen for cdt1 degradation by thecul4-ddb1 ubiquitin ligase in response to DNA damage. J Biol Chem 281: 3753-3756.
47. Hu J, McCall CM, Ohta T, Xiong Y. 2004. Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Nat Cell Biol 6: 1003-1009.
48. Hu J, Zacharek S, He YJ, Lee H, Shumway S, Duronio RJ, Xiong Y. 2008. WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase. Genes Dev 22: 866-871.
49. Ishii T, Shiomi Y, Takami T, Murakami Y, Ohnishi N, Nishitani H. 2010. Proliferating cell nuclear antigen-dependent rapid recruitment of Cdt1 and CRL4Cdt2 at DNA-damaged sites after UV irradiation in HeLa cells. J Biol Chem 285: 41993-42000.
50. Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG Jr. 2001. HIFa targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science 292: 464-468.
51. Jaakkola P, Mole DR, Tian YM, Wilson MI, Gielbert J, Gaskell SJ, Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, et al. 2001. Targeting of HIF-a to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292: 468-472.
52. Jackson S, Xiong Y. 2009. CRL4s: the CUL4-RING E3 ubiquitin ligases. Trends Biochem Sci 34: 562-570.
53. Jaspersen SL, Charles JF, Morgan DO. 1999. Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase Cdc28 and the phosphatase Cdc14. Curr Biol 9: 227-236.
54. Jin J, Arias EE, Chen J, Harper JW, Walter JC. 2006. A family of diverse Cul4-Ddb1-interacting proteins includes Cdt2, which is required for S phase destruction of the replication factor Cdt1. Mol Cell 23: 709-721.
55. Jin L, Williamson A, Banerjee S, Philipp I, Rape M. 2008. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell 133: 653-665.
56. Jorgensen S, Eskildsen M, Fugger K, Hansen L, Larsen MS, Kousholt AN, Syljuasen RG, Trelle MB, Jensen ON, Helin K, et al. 2011. SET8 is degraded via PCNA-coupled CRL4(CDT2) ubiquitylation in S phase and after UV irradiation. J Cell Biol 192: 43-54.
57. Kerns SL, Torke SJ, Benjamin JM, McGarry TJ. 2007. Geminin prevents rereplication during Xenopus development. J Biol Chem 282: 5514-5521.
58. Kim Y, Kipreos ET. 2007. The Caenorhabditis elegans replication licensing factor CDT-1 is targeted for degradation by the CUL-4/DDB-1 complex. Mol Cell Biol 27: 1394-1406.
59. Kim SH, Michael WM. 2008. Regulated proteolysis of DNA polymerase h during the DNA-damage response in C. elegans. Mol Cell 32: 757-766.
60. Kim J, Feng H, Kipreos ET. 2007. C. elegans CUL-4 prevents rereplication by promoting the nuclear export of CDC-6 via a CKI-1-dependent pathway. Curr Biol 17: 966-972.
61. Kim Y, Starostina NG, Kipreos ET. 2008. The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to control replication licensing. Genes Dev 22: 2507-2519.
62. Kim DH, Budhavarapu VN, Herrera CR, Nam HW, Kim YS, Yew PR. 2010. The CRL4Cdt2 ubiquitin ligase mediates the proteolysis of cyclin-dependent kinase inhibitor Xic1 through a direct association with PCNA. Mol Cell Biol 30: 4120-4133.
63. Komander D. 2009. The emerging complexity of protein ubiquitination. Biochem Soc Trans 37: 937-953.
64. Kondo T, Kobayashi M, Tanaka J, Yokoyama A, Suzuki S, Kato N, Onozawa M, Chiba K, Hashino S, Imamura M, et al. 2004. Rapid degradation of Cdt1 upon UV-induced DNA damage is mediated by SCFSkp2 complex. J Biol Chem 279: 27315-27319.
65. Kraft C, Herzog F, Gieffers C, Mechtler K, Hagting A, Pines J, Peters JM. 2003. Mitotic regulation of the human anaphasepromoting complex by phosphorylation. EMBO J 22: 6598-6609.
66. Kramer ER, Scheuringer N, Podtelejnikov AV, Mann M, Peters JM. 2000. Mitotic regulation of the APC activator proteins CDC20 and CDH1. Mol Biol Cell 11: 1555-1569.
67. Lee JY, Yu SJ, Park YG, Kim J, Sohn J. 2007. Glycogen synthase kinase 3b phosphorylates p21WAF1/CIP1 for proteasomal degradation after UV irradiation. Mol Cell Biol 27: 3187-3198.
68. Lee JH, Terzaghi W, Gusmaroli G, Charron JB, Yoon HJ, Chen H, He YJ, Xiong Y, Deng XW. 2008. Characterization of Arabidopsis and rice DWD proteins and their roles as substrate receptors for CUL4-RING E3 ubiquitin ligases. Plant Cell 20: 152-167.
69. Lee HO, Zacharek SJ, Xiong Y, Duronio RJ. 2010. Cell typedependent requirement for PIP box-regulated Cdt1 destruction during S phase. Mol Biol Cell 21: 3639-3653.
70. Li A, Blow JJ. 2005. Cdt1 downregulation by proteolysis and geminin inhibition prevents DNA re-replication in Xenopus. EMBO J 24: 395-404.
71. Li Y, Dowbenko D, Lasky LA. 2002. AKT/PKB phosphorylation of p21Cip/WAF1 enhances protein stability of p21Cip/WAF1 and promotes cell survival. J Biol Chem 277: 11352-11361.
72. Li X, Zhao Q, Liao R, Sun P, Wu X. 2003. The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation. J Biol Chem 278: 30854-30858.
73. Lin JJ, Milhollen MA, Smith PG, Narayanan U, Dutta A. 2010. NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells. Cancer Res 70: 10310-10320.
74. Liu C, Powell KA, Mundt K, Wu L, Carr AM, Caspari T. 2003. Cop9/signalosome subunits and Pcu4 regulate ribonucleotide reductase by both checkpoint-dependent and-independent mechanisms. Genes Dev 17: 1130-1140.
75. Liu C, Poitelea M, Watson A, Yoshida SH, Shimoda C, Holmberg C, Nielsen O, Carr AM. 2005. Transactivation of Schizosaccharomyces pombe cdt2+ stimulates a Pcu4-Ddb1-CSN ubiquitin ligase. EMBO J 24: 3940-3951.
76. Liu CL, Yu IS, Pan HW, Lin SW, Hsu HC. 2007. L2dtl is essential for cell survival and nuclear division in early mouse embryonic development. J Biol Chem 282: 1109-1118.
77. Liu P, Slater DM, Lenburg M, Nevis K, Cook JG, Vaziri C. 2009. Replication licensing promotes cyclin D1 expression and G1 progression in untransformed human cells. Cell Cycle 8: 125-136.
78. Machida YJ, Teer JK, Dutta A. 2005. Acute reduction of an origin recognition complex (ORC) subunit in human cells reveals a requirement of ORC for Cdk2 activation. J Biol Chem 280: 27624-27630.
79. Mailand N, Diffley JF. 2005. CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis. Cell 122: 915-926.
80. McCall CM, Miliani de Marval PL, Chastain PD 2nd, Jackson SC, He YJ, Kotake Y, Cook JG, Xiong Y. 2008. Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development. Mol Cell Biol 28: 5621-5633.
81. Medema RH, Klompmaker R, Smits VA, Rijksen G. 1998. p21waf1 can block cells at two points in the cell cycle, butdoes not interfere with processive DNA-replication or stressactivated kinases. Oncogene 16: 431-441.
82. Michishita M, Morimoto A, Ishii T, Komori H, Shiomi Y, Higuchi Y, Nishitani H. 2011. Positively charged residues located downstream of PIP box, together with TD amino acids within PIP box, are important for CRL4(Cdt2)-mediated proteolysis. Genes Cells 16: 12-22.
83. Milhollen MA, Narayanan U, Soucy TA, Veiby PO, Smith PG, Amidon B. 2011. Inhibition of NEDD8-activating enzyme induces rereplication and apoptosis in human tumor cells consistent with deregulating CDT1 turnover. Cancer Res 71: 3042-3051.
84. Min JH, Yang H, Ivan M, Gertler F, Kaelin WG Jr, Pavletich NP. 2002. Structure of an HIF-1a-pVHL complex: hydroxyproline recognition in signaling. Science 296: 1886-1889.
85. Mizushima T, Yoshida Y, Kumanomidou T, Hasegawa Y, Suzuki A, Yamane T, Tanaka K. 2007. Structural basis for the selection of glycosylated substrates by SCF(Fbs1) ubiquitin ligase. Proc Natl Acad Sci 104: 5777-5781.
86. Mockaitis K, Estelle M. 2008. Auxin receptors and plant development: a new signaling paradigm. Annu Rev Cell Dev Biol 24: 55-80.
87. Moldovan GL, Pfander B, Jentsch S. 2007. PCNA, the maestro of the replication fork. Cell 129: 665-679.
88. Moss J, Tinline-Purvis H, Walker CA, Folkes LK, Stratford MR, Hayles J, Hoe KL, Kim DU, Park HO, Kearsey SE, et al. 2010. Break-induced ATR and Ddb1-Cul4(Cdt)(2) ubiquitin ligasedependent nucleotide synthesis promotes homologous recombination repair in fission yeast. Genes Dev 24: 2705-2716.
89. Nakanishi M, Robetorye RS, Pereira-Smith OM, Smith JR. 1995. The C-terminal region of p21SDI1/WAF1/CIP1 is involved in proliferating cell nuclear antigen binding but does not appear to be required for growth inhibition. J Biol Chem 270: 17060-17063.
90. Nestoras K, Mohammed AH, Schreurs AS, Fleck O, Watson AT, Poitelea M, O'Shea C, Chahwan C, Holmberg C, Kragelund BB, et al. 2010. Regulation of ribonucleotide reductase by Spd1 involves multiple mechanisms. Genes Dev 24: 1145-1159.
91. Niculescu AB III, Chen X, Smeets M, Hengst L, Prives C, Reed SI. 1998. Effects of p21(Cip1/Waf1) at both the G1/S and the G2/M cell cycle transitions: pRb is a critical determinant in blocking DNA replication and in preventing endoreduplication. Mol Cell Biol 18: 629-643.
92. Nishitani H, Lygerou Z, Nishimoto T. 2004. Proteolysis of DNA replication licensing factor Cdt1 in S-phase is performed independently of Geminin through its N-terminal region. J Biol Chem 279: 30807-30816.
93. Nishitani H, Sugimoto N, Roukos V, Nakanishi Y, Saijo M, Obuse C, Tsurimoto T, Nakayama KI, Nakayama K, Fujita M, et al. 2006. Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. EMBO J 25: 1126-1136.
94. Nishitani H, Shiomi Y, Iida H, Michishita M, Takami T, Tsurimoto T. 2008. 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 283: 29045-29052.
95. O'Connell BC, Harper JW. 2007. Ubiquitin proteasome system (UPS): what can chromatin do for you? Curr Opin Cell Biol 19: 206-214.
96. Oda H, Hubner MR, Beck DB, Vermeulen M, Hurwitz J, Spector DL, Reinberg D. 2010. Regulation of the histone H4 monomethylase PR-Set7 by CRL4(Cdt2)-mediated PCNA-dependent degradation during DNA damage. Mol Cell 40: 364-376.
97. Perry JJ, Tainer JA, Boddy MN. 2008. A SIM-ultaneous role for SUMO and ubiquitin. Trends Biochem Sci 33: 201-208.
98. Pfleger CM, Lee E, Kirschner MW. 2001. Substrate recognition by the Cdc20 and Cdh1 components of the anaphase-promoting complex. Genes Dev 15: 2396-2407.
99. Ralph E, Boye E, Kearsey SE. 2006. DNA damage induces Cdt1 proteolysis in fission yeast via a pathway dependent on Cdt2 and Ddb1. EMBO Rep 7: 1134-1139.
100. Raman M, Havens CG, Walter JC, Harper JW. 2011. A genome wide screen identifies p97 as an essential regulator of DNA damage-dependent CDT1 destruction. Mol Cell (in press).
101. Ravid T, Hochstrasser M. 2008. Diversity of degradation signals in the ubiquitin-proteasome system. Nat Rev Mol Cell Biol 9: 679-690.
102. Rice JC, Nishioka K, Sarma K, Steward R, Reinberg D, Allis CD. 2002. Mitotic-specific methylation of histone H4 Lys 20 follows increased PR-Set7 expression and its localization to mitotic chromosomes. Genes Dev 16: 2225-2230.
103. Rodrigo-Brenni MC, Foster SA, Morgan DO. 2010. Catalysis of lysine 48-specific ubiquitin chain assembly by residues in E2 and ubiquitin. Mol Cell 39: 548-559.
104. Roukos V, Kinkhabwala A, Colombelli J, Kotsantis P, Taraviras S, Nishitani H, Stelzer E, Bastiaens P, Lygerou Z. 2011. Dynamic recruitment of licensing factor Cdt1 to sites of DNA damage. J Cell Sci 124: 422-434.
105. Saha A, Lewis S, Kleiger G, Kuhlman B, Deshaies RJ. 2011. Essential role for ubiquitin-ubiquitin-conjugating enzyme interaction in ubiquitin discharge from Cdc34 to substrate. Mol Cell 42: 75-83.
106. Sansam CL, Shepard JL, Lai K, Ianari A, Danielian PS, Amsterdam A, Hopkins N, Lees JA. 2006. DTL/CDT2 is essential for both CDT1 regulation and the early G2/M checkpoint. Genes & Dev 20: 3117-3129.
107. Scott MT, Morrice N, Ball KL. 2000. Reversible phosphorylation at the C-terminal regulatory domain of p21(Waf1/Cip1) modulates proliferating cell nuclear antigen binding. J Biol Chem 275: 11529-11537.
108. Scrima A, Konickova R, Czyzewski BK, Kawasaki Y, Jeffrey PD, Groisman R, Nakatani Y, Iwai S, Pavletich NP, Thoma NH. 2008. Structural basis of UV DNA-damage recognition by the DDB1-DDB2 complex. Cell 135: 1213-1223.
109. Senga T, Sivaprasad U, Zhu W, Park JH, Arias EE, Walter JC, Dutta A. 2006. PCNA is a co-factor for Cdt1 degradation by CUL4/DDB1 mediated N-terminal ubiquitination. J Biol Chem 281: 6246-6252.
110. Shibata E, Abbas T, Huang X, Wohlschlegel JA, Dutta A. 2011. Selective ubiquitylation of p21 and Cdt1 by UBCH8 and UBE2G ubiquitin conjugating enzymes via the CRL4Cdt2 ubiquitin ligase complex. Mol Cell Biol doi: 10.1128/ MCB.05496-11
111. Shibutani ST, de la Cruz AF, Tran V, Turbyfill WJ III, Reis T, Edgar BA, Duronio RJ. 2008. Intrinsic negative cell cycle regulation provided by PIP box-and Cul4Cdt2-mediated destruction of E2f1 during S phase. Dev Cell 15: 890-900.
112. Soria G, Speroni J, Podhajcer OL, Prives C, Gottifredi V. 2008. p21 differentially regulates DNA replication and DNA-repair-associated processes after UV irradiation. J Cell Sci 121: 3271-3282.
113. Soucy TA, Smith PG, Milhollen MA, Berger AJ, Gavin JM, Adhikari S, Brownell JE, Burke KE, Cardin DP, Critchley S, et al. 2009. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 458: 732-736.
114. Stuart SA, Wang JY. 2009. Ionizing radiation induces ATMindependent degradation of p21Cip1 in transformed cells. J Biol Chem 284: 15061-15070.
115. Sugasawa K, Okuda Y, Saijo M, Nishi R, Matsuda N, Chu G, Mori T, Iwai S, Tanaka K, Tanaka K, et al. 2005. UV-inducedubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex. Cell 121: 387-400.
116. Takeda DY, Parvin JD, Dutta A. 2005. Degradation of Cdt1 during S phase is Skp2-independent and is required for efficient progression of mammalian cells through S phase. J Biol Chem 280: 23416-23423.
117. Tan X, Zheng N. 2009. Hormone signaling through protein destruction: a lesson from plants. Am J Physiol Endocrinol Metab 296: E223-E227. doi: 10.1152/ajpendo.90807.2008
118. Tardat M, Brustel J, Kirsh O, Lefevbre C, Callanan M, Sardet C, Julien E. 2010. The histone H4 Lys 20 methyltransferase PRSet7 regulates replication origins in mammalian cells. Nat Cell Biol 12: 1086-1093.
119. Teer JK, Machida YJ, Labit H, Novac O, Hyrien O, Marheineke K, Zannis-Hadjopoulos M, Dutta A. 2006. Proliferating human cells hypomorphic for origin recognition complex 2 and pre-replicative complex formation have a defect in p53 activation and Cdk2 kinase activation. J Biol Chem 281: 6253-6260.
120. Terai K, Abbas T, Jazaeri AA, Dutta A. 2010. CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to promote translesion DNA synthesis. Mol Cell 37: 143-149.
121. Vaziri C, Saxena S, Jeon Y, Lee C, Murata K, Machida Y, Wagle N, Hwang DS, Dutta A. 2003. A p53-dependent checkpoint pathway prevents rereplication. Mol Cell 11: 997-1008.
122. Waga S, Zembutsu A. 2006. Dynamics of DNA binding of replication initiation proteins during de novo formation of pre-replicative complexes in Xenopus egg extracts. J Biol Chem 281: 10926-10934.
123. Wang W, Nacusi L, Sheaff RJ, Liu X. 2005. Ubiquitination of p21Cip1/WAF1 by SCFSkp2: substrate requirement and ubiquitination site selection. Biochemistry 44: 14553-14564.
124. Wang SC, Nakajima Y, Yu YL, Xia W, Chen CT, Yang CC, McIntush EW, Li LY, Hawke DH, Kobayashi R, et al. 2006. Tyrosine phosphorylation controls PCNA function through protein stability. Nat Cell Biol 8: 1359-1368.
125. Warbrick E, Lane DP, Glover DM, Cox LS. 1995. A small peptide inhibitor of DNA replication defines the site of interaction between the cyclin-dependent kinase inhibitor p21WAF1 and proliferating cell nuclear antigen. Curr Biol 5: 275-282.
126. Wickliffe KE, Lorenz S, Wemmer DE, Kuriyan J, Rape M. 2011. The mechanism of linkage-specific ubiquitin chain elongation by a single-subunit E2. Cell 144: 769-781.
127. Wu S, Rice JC. 2011. A new regulator of the cell cycle: the PRSet7 histone methyltransferase. Cell Cycle 10: 68-72.
128. Wu S, Wang W, Kong X, Congdon LM, Yokomori K, Kirschner MW, Rice JC. 2010. Dynamic regulation of the PR-Set7 histone methyltransferase is required for normal cell cycle progression. Genes Dev 24: 2531-2542.
129. Xu H, Wang J, Hu Q, Quan Y, Chen H, Cao Y, Li C, Wang Y, He Q. 2010. DCAF26, an adaptor protein of Cul4-based E3, is essential for DNA methylation in Neurospora crassa. PLoS Genet 6: doi: 10.1371/journal.pgen.1001132.
130. Ye Y, Rape M. 2009. Building ubiquitin chains: E2 enzymes at work. Nat Rev Mol Cell Biol 10: 755-764.
131. Yen HC, Elledge SJ. 2008. Identification of SCF ubiquitin ligase substrates by global protein stability profiling. Science 322: 923-929.
132. Yen HC, Xu Q, Chou DM, Zhao Z, Elledge SJ. 2008. Global protein stability profiling in mammalian cells. Science 322: 918-923.
133. Yin Y, Yu VC, Zhu G, Chang DC. 2008. SET8 plays a role in controlling G1/S transition by blocking lysine acetylation in histone through binding to H4 N-terminal tail. Cell Cycle 7: 1423-1432.
134. Yoshida Y, Chiba T, Tokunaga F, Kawasaki H, Iwai K, Suzuki T, Ito Y, Matsuoka K, Yoshida M, Tanaka K, et al. 2002. E3 ubiquitin ligase that recognizes sugar chains. Nature 418: 438-442.
135. Yoshida K, Takisawa H, Kubota Y. 2005. Intrinsic nuclear import activity of geminin is essential to prevent re-initiation of DNA replication in Xenopus eggs. Genes Cells 10: 63-73.
136. You Z, Harvey K, Kong L, Newport J. 2002. Xic1 degradation in Xenopus egg extracts is coupled to initiation of DNA replication. Genes Dev 16: 1182-1194.
137. Yu ZK, Gervais JL, Zhang H. 1998. Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21(CIP1/WAF1) and cyclin D proteins. Proc Natl Acad Sci 95: 11324-11329.
138. Zachariae W, Schwab M, Nasmyth K, Seufert W. 1998. Control of cyclin ubiquitination by CDK-regulated binding of Hct1 to the anaphase promoting complex. Science 282: 1721-1724.
139. Zaidi IW, Rabut G, Poveda A, Scheel H, Malmstrom J, Ulrich H, Hofmann K, Pasero P, Peter M, Luke B. 2008. Rtt101 and Mms1 in budding yeast form a CUL4(DDB1)-like ubiquitin ligase that promotes replication through damaged DNA. EMBO Rep 9: 1034-1040.
140. Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, et al. 2002. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature 416: 703-709.
141. Zhong W, Feng H, Santiago FE, Kipreos ET. 2003. CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication licensing. Nature 423: 885-889.