#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Distinct and sequential re-replication barriers ensure precise genome duplication


Autoři: Yizhuo Zhou aff001;  Pedro N. Pozo aff002;  Seeun Oh aff003;  Haley M. Stone aff001;  Jeanette Gowen Cook aff001
Působiště autorů: Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United State of America aff001;  Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United State of America aff002;  F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute and the Research Division of Immunology, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, United State of America aff003;  Lineberger Comprehensive Cancer, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United State of America aff004
Vyšlo v časopise: Distinct and sequential re-replication barriers ensure precise genome duplication. PLoS Genet 16(8): e32767. doi:10.1371/journal.pgen.1008988
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008988

Souhrn

Achieving complete and precise genome duplication requires that each genomic segment be replicated only once per cell division cycle. Protecting large eukaryotic genomes from re-replication requires an overlapping set of molecular mechanisms that prevent the first DNA replication step, the DNA loading of MCM helicase complexes to license replication origins, after S phase begins. Previous reports have defined many such origin licensing inhibition mechanisms, but the temporal relationships among them are not clear, particularly with respect to preventing re-replication in G2 and M phases. Using a combination of mutagenesis, biochemistry, and single cell analyses in human cells, we define a new mechanism that prevents re-replication through hyperphosphorylation of the essential MCM loading protein, Cdt1. We demonstrate that Cyclin A/CDK1 can hyperphosphorylate Cdt1 to inhibit MCM re-loading in G2 phase. The mechanism of inhibition is to block Cdt1 binding to MCM independently of other known Cdt1 inactivation mechanisms such as Cdt1 degradation during S phase or Geminin binding. Moreover, our findings suggest that Cdt1 dephosphorylation at the mitosis-to-G1 phase transition re-activates Cdt1. We propose that multiple distinct, non-redundant licensing inhibition mechanisms act in a series of sequential relays through each cell cycle phase to ensure precise genome duplication.

Klíčová slova:

Cell cycle and cell division – Cyclins – DNA replication – G1 phase – Immunoblotting – Phosphorylation – Synthesis phase – G2 phase


Zdroje

1. Parker MW, Botchan MR, Berger JM. Mechanisms and regulation of DNA replication initiation in eukaryotes. Crit Rev Biochem Mol Biol. 2017;52(2):107–44. Epub 2017/01/18. doi: 10.1080/10409238.2016.1274717 28094588; PubMed Central PMCID: PMC5545932.

2. Masai H, Matsumoto S, You Z, Yoshizawa-Sugata N, Oda M. Eukaryotic chromosome DNA replication: where, when, and how? Annu Rev Biochem. 2010;79:89–130. Epub 2010/04/09. doi: 10.1146/annurev.biochem.052308.103205 20373915.

3. Siddiqui K, On KF, Diffley JF. Regulating DNA replication in eukarya. Cold Spring Harb Perspect Biol. 2013;5(9). doi: 10.1101/cshperspect.a012930 23838438; PubMed Central PMCID: PMC3753713.

4. Arias EE, Walter JC. Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells. Genes Dev. 2007;21(5):497–518. Epub 2007/03/09. doi: 10.1101/gad.1508907 17344412.

5. Mechali M. Eukaryotic DNA replication origins: many choices for appropriate answers. Nat Rev Mol Cell Biol. 2010;11(10):728–38. Epub 2010/09/24. doi: 10.1038/nrm2976 20861881.

6. Li C, Jin J. DNA replication licensing control and rereplication prevention. Protein & cell. 2010;1(3):227–36. doi: 10.1007/s13238-010-0032-z 21203969.

7. Truong LN, Wu X. Prevention of DNA re-replication in eukaryotic cells. Journal of molecular cell biology. 2011;3(1):13–22. doi: 10.1093/jmcb/mjq052 21278447; PubMed Central PMCID: PMC3030972.

8. Hook SS, Lin JJ, Dutta A. Mechanisms to control rereplication and implications for cancer. Curr Opin Cell Biol. 2007;19(6):663–71. Epub 2007/12/07. doi: 10.1016/j.ceb.2007.10.007 18053699; PubMed Central PMCID: PMC2174913.

9. Blow JJ, Gillespie PJ. Replication licensing and cancer—a fatal entanglement? Nature reviews. 2008;8(10):799–806. doi: 10.1038/nrc2500 18756287; PubMed Central PMCID: PMC2577763.

10. Munoz S, Bua S, Rodriguez-Acebes S, Megias D, Ortega S, de Martino A, et al. In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias. Cell Rep. 2017;19(5):928–38. doi: 10.1016/j.celrep.2017.04.032 28467906.

11. Pozo PN, Cook JG. Regulation and Function of Cdt1; A Key Factor in Cell Proliferation and Genome Stability. Genes (Basel). 2016;8(1). doi: 10.3390/genes8010002 28025526.

12. Borlado LR, Mendez J. CDC6: from DNA replication to cell cycle checkpoints and oncogenesis. Carcinogenesis. 2008;29(2):237–43. Epub 2007/12/01. doi: 10.1093/carcin/bgm268 18048387.

13. Reusswig KU, Pfander B. Control of Eukaryotic DNA Replication Initiation-Mechanisms to Ensure Smooth Transitions. Genes (Basel). 2019;10(2). Epub 2019/02/01. doi: 10.3390/genes10020099 30700044; PubMed Central PMCID: PMC6409694.

14. Hills SA, Diffley JF. DNA replication and oncogene-induced replicative stress. Curr Biol. 2014;24(10):R435–44. Epub 2014/05/23. doi: 10.1016/j.cub.2014.04.012 24845676.

15. Brustel J, Tardat M, Kirsh O, Grimaud C, Julien E. Coupling mitosis to DNA replication: the emerging role of the histone H4-lysine 20 methyltransferase PR-Set7. Trends in cell biology. 2011;21(8):452–60. Epub 2011/06/03. doi: 10.1016/j.tcb.2011.04.006 21632252.

16. Nishitani H, Taraviras S, Lygerou Z, Nishimoto T. The human licensing factor for DNA replication Cdt1 accumulates in G1 and is destabilized after initiation of S-phase. J Biol Chem. 2001;276(48):44905–11. Epub 2001/09/14. doi: 10.1074/jbc.M105406200 11555648.

17. Chandrasekaran S, Tan TX, Hall JR, Cook JG. Stress-stimulated mitogen-activated protein kinases control the stability and activity of the Cdt1 DNA replication licensing factor. Mol Cell Biol. 2011;31(22):4405–16. Epub 2011/09/21. doi: 10.1128/MCB.06163-11 21930785; PubMed Central PMCID: PMC3209262.

18. Ballabeni A, Melixetian M, Zamponi R, Masiero L, Marinoni F, Helin K. Human geminin promotes pre-RC formation and DNA replication by stabilizing CDT1 in mitosis. EMBO J. 2004;23(15):3122–32. Epub 2004/07/17. doi: 10.1038/sj.emboj.7600314 15257290; PubMed Central PMCID: PMC514931.

19. Coulombe P, Gregoire D, Tsanov N, Mechali M. A spontaneous Cdt1 mutation in 129 mouse strains reveals a regulatory domain restraining replication licensing. Nat Commun. 2013;4:2065. Epub 2013/07/03. doi: 10.1038/ncomms3065 23817338.

20. Rizzardi LF, Coleman KE, Varma D, Matson JP, Oh S, Cook JG. CDK1-dependent inhibition of the E3 ubiquitin ligase CRL4CDT2 ensures robust transition from S Phase to Mitosis. J Biol Chem. 2015;290(1):556–67. doi: 10.1074/jbc.M114.614701 25411249; PubMed Central PMCID: PMC4281756.

21. Varma D, Chandrasekaran S, Sundin LJ, Reidy KT, Wan X, Chasse DA, et al. Recruitment of the human Cdt1 replication licensing protein by the loop domain of Hec1 is required for stable kinetochore-microtubule attachment. Nat Cell Biol. 2012;14(6):593–603. Epub 2012/05/15. doi: 10.1038/ncb2489 22581055; PubMed Central PMCID: PMC3366049.

22. Yanagi KI, Mizuno T, You Z, Hanaoka F. Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity. J Biol Chem. 2002;277(43):40871–80. doi: 10.1074/jbc.M206202200 12192004

23. Cook JG, Chasse DA, Nevins JR. The regulated association of Cdt1 with minichromosome maintenance proteins and Cdc6 in mammalian cells. J Biol Chem. 2004;279(10):9625–33. Epub 2003/12/16. doi: 10.1074/jbc.M311933200 14672932.

24. Wohlschlegel JA, Dwyer BT, Dhar SK, Cvetic C, Walter JC, Dutta A. Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science. 2000;290(5500):2309–12. doi: 10.1126/science.290.5500.2309 11125146.

25. Parker MW, Bell M, Mir M, Kao JA, Darzacq X, Botchan MR, et al. A new class of disordered elements controls DNA replication through initiator self-assembly. eLife. 2019;8. Epub 2019/09/29. doi: 10.7554/eLife.48562 31560342.

26. Khayrutdinov BI, Bae WJ, Yun YM, Lee JH, Tsuyama T, Kim JJ, et al. Structure of the Cdt1 C-terminal domain: conservation of the winged helix fold in replication licensing factors. Protein Sci. 2009;18(11):2252–64. doi: 10.1002/pro.236 19722278; PubMed Central PMCID: PMC2788280.

27. Lee C, Hong B, Choi JM, Kim Y, Watanabe S, Ishimi Y, et al. Structural basis for inhibition of the replication licensing factor Cdt1 by geminin. Nature. 2004;430(7002):913–7. doi: 10.1038/nature02813 15286659.

28. Pozo PN, Matson JP, Cole Y, Kedziora KM, Grant GD, Temple B, et al. Cdt1 variants reveal unanticipated aspects of interactions with Cyclin/CDK and MCM important for normal genome replication. Mol Biol Cell. 2018:mbcE18040242. Epub 2018/10/04. doi: 10.1091/mbc.E18-04-0242 30281379; PubMed Central PMCID: PMC6333176.

29. Ferenbach A, Li A, Brito-Martins M, Blow JJ. Functional domains of the Xenopus replication licensing factor Cdt1. Nucleic Acids Res. 2005;33(1):316–24. Epub 2005/01/18. doi: 10.1093/nar/gki176 15653632; PubMed Central PMCID: PMC546161.

30. Teer JK, Dutta A. Human Cdt1 lacking the evolutionarily conserved region that interacts with MCM2-7 is capable of inducing re-replication. The Journal of biological chemistry. 2008;283(11):6817–25. Epub 2008/01/11. doi: 10.1074/jbc.M708767200 18184650.

31. Zhang J, Yu L, Wu X, Zou L, Sou KK, Wei Z, et al. The interacting domains of hCdt1 and hMcm6 involved in the chromatin loading of the MCM complex in human cells. Cell Cycle. 2010;9(24):4848–57. Epub 2010/11/26. doi: 10.4161/cc.9.24.14136 21099365.

32. You Z, Ode KL, Shindo M, Takisawa H, Masai H. Characterization of conserved arginine residues on Cdt1 that affect licensing activity and interaction with Geminin or Mcm complex. Cell Cycle. 2016:0. doi: 10.1080/15384101.2015.1106652 26940553.

33. Vaziri C, Saxena S, Jeon Y, Lee C, Murata K, Machida Y, et al. A p53-dependent checkpoint pathway prevents rereplication. Mol Cell. 2003;11(4):997–1008. doi: 10.1016/s1097-2765(03)00099-6 12718885.

34. Nishitani H, Sugimoto N, Roukos V, Nakanishi Y, Saijo M, Obuse C, et al. Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. EMBO J. 2006;25(5):1126–36. Epub 2006/02/17. doi: 10.1038/sj.emboj.7601002 16482215; PubMed Central PMCID: PMC1409712.

35. Zhu W, Chen Y, Dutta A. Rereplication by depletion of geminin is seen regardless of p53 status and activates a G2/M checkpoint. Mol Cell Biol. 2004;24(16):7140–50. Epub 2004/07/30. doi: 10.1128/MCB.24.16.7140-7150.2004 15282313; PubMed Central PMCID: PMC479725.

36. Melixetian M, Ballabeni A, Masiero L, Gasparini P, Zamponi R, Bartek J, et al. Loss of Geminin induces rereplication in the presence of functional p53. J Cell Biol. 2004;165(4):473–82. doi: 10.1083/jcb.200403106 15159417.

37. Klotz-Noack K, McIntosh D, Schurch N, Pratt N, Blow JJ. Re-replication induced by geminin depletion occurs from G2 and is enhanced by checkpoint activation. J Cell Sci. 2012;125(Pt 10):2436–45. doi: 10.1242/jcs.100883 22366459; PubMed Central PMCID: PMC3481538.

38. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Nucleic Acids Res. 2015;43(Database issue):D512–20. Epub 2014/12/18. doi: 10.1093/nar/gku1267 25514926; PubMed Central PMCID: PMC4383998.

39. Sugimoto N, Tatsumi Y, Tsurumi T, Matsukage A, Kiyono T, Nishitani H, et al. Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding. J Biol Chem. 2004;279(19):19691–7. Epub 2004/03/03. doi: 10.1074/jbc.M313175200 14993212.

40. Takeda DY, Parvin JD, Dutta A. Degradation of Cdt1 during S phase is Skp2-independent and is required for efficient progression of mammalian cells through S phase. J Biol Chem. 2005;280(24):23416–23. doi: 10.1074/jbc.M501208200 15855168.

41. Miotto B, Struhl K. JNK1 phosphorylation of Cdt1 inhibits recruitment of HBO1 histone acetylase and blocks replication licensing in response to stress. Mol Cell. 2011;44(1):62–71. Epub 2011/08/23. doi: 10.1016/j.molcel.2011.06.021 21856198; PubMed Central PMCID: PMC3190045.

42. Matson JP, Dumitru R, Coryell P, Baxley RM, Chen W, Twaroski K, et al. Rapid DNA replication origin licensing protects stem cell pluripotency. eLife. 2017;6. Epub 2017/11/18. doi: 10.7554/eLife.30473 29148972; PubMed Central PMCID: PMC5720591.

43. Haland TW, Boye E, Stokke T, Grallert B, Syljuasen RG. Simultaneous measurement of passage through the restriction point and MCM loading in single cells. Nucleic Acids Res. 2015. doi: 10.1093/nar/gkv744 26250117.

44. Kinoshita E, Kinoshita-Kikuta E, Takiyama K, Koike T. Phosphate-binding tag, a new tool to visualize phosphorylated proteins. Mol Cell Proteomics. 2006;5(4):749–57. Epub 2005/12/13. doi: 10.1074/mcp.T500024-MCP200 16340016.

45. Higa LA, Mihaylov IS, Banks DP, Zheng J, Zhang H. Radiation-mediated proteolysis of CDT1 by CUL4-ROC1 and CSN complexes constitutes a new checkpoint. Nat Cell Biol. 2003;5(11):1008–15. Epub 2003/10/28. doi: 10.1038/ncb1061 14578910.

46. Hu J, McCall CM, Ohta T, Xiong Y. Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage. Nat Cell Biol. 2004;6(10):1003–9. doi: 10.1038/ncb1172 15448697.

47. Arias EE, Walter JC. Replication-dependent destruction of Cdt1 limits DNA replication to a single round per cell cycle in Xenopus egg extracts. Genes Dev. 2005;19(1):114–26. doi: 10.1101/gad.1255805 15598982.

48. Hall FL, Vulliet PR. Proline-directed protein phosphorylation and cell cycle regulation. Curr Opin Cell Biol. 1991;3(2):176–84. Epub 1991/04/01. doi: 10.1016/0955-0674(91)90136-m 1831990.

49. Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol Mol Biol Rev. 2004;68(2):320–44. Epub 2004/06/10. doi: 10.1128/MMBR.68.2.320-344.2004 15187187; PubMed Central PMCID: PMC419926.

50. Songyang Z, Lu KP, Kwon YT, Tsai LH, Filhol O, Cochet C, et al. A structural basis for substrate specificities of protein Ser/Thr kinases: primary sequence preference of casein kinases I and II, NIMA, phosphorylase kinase, calmodulin-dependent kinase II, CDK5, and Erk1. Mol Cell Biol. 1996;16(11):6486–93. Epub 1996/11/01. doi: 10.1128/mcb.16.11.6486 8887677; PubMed Central PMCID: PMC231650.

51. Echalier A, Endicott JA, Noble ME. Recent developments in cyclin-dependent kinase biochemical and structural studies. Biochim Biophys Acta. 2010;1804(3):511–9. Epub 2009/10/14. doi: 10.1016/j.bbapap.2009.10.002 19822225.

52. Faust D, Dolado I, Cuadrado A, Oesch F, Weiss C, Nebreda AR, et al. p38alpha MAPK is required for contact inhibition. Oncogene. 2005;24(53):7941–5. Epub 2005/07/20. doi: 10.1038/sj.onc.1208948 16027723.

53. Swat A, Dolado I, Rojas JM, Nebreda AR. Cell Density-Dependent Inhibition of Epidermal Growth Factor Receptor Signaling by p38{alpha} Mitogen-Activated Protein Kinase via Sprouty2 Downregulation. Mol Cell Biol. 2009;29(12):3332–43. doi: 10.1128/MCB.01955-08 19364817

54. Cha H, Wang X, Li H, Fornace AJ. A Functional Role for p38 MAPK in Modulating Mitotic Transit in the Absence of Stress. Journal of Biological Chemistry. 2007;282(31):22984–92. doi: 10.1074/jbc.M700735200 17548358

55. Yaffe MB, Schutkowski M, Shen M, Zhou XZ, Stukenberg PT, Rahfeld JU, et al. Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism. Science. 1997;278(5345):1957–60. Epub 1998/01/07. doi: 10.1126/science.278.5345.1957 9395400.

56. Mailand N, Diffley JF. CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis. Cell. 2005;122(6):915–26. doi: 10.1016/j.cell.2005.08.013 16153703.

57. Vassilev LT, Tovar C, Chen S, Knezevic D, Zhao X, Sun H, et al. Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1. Proc Natl Acad Sci U S A. 2006;103(28):10660–5. Epub 2006/07/05. doi: 10.1073/pnas.0600447103 16818887; PubMed Central PMCID: PMC1502288.

58. McGarry TJ, Kirschner MW. Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell. 1998;93(6):1043–53. doi: 10.1016/s0092-8674(00)81209-x 9635433.

59. Bollen M, Peti W, Ragusa MJ, Beullens M. The extended PP1 toolkit: designed to create specificity. Trends Biochem Sci. 2010;35(8):450–8. Epub 2010/04/20. doi: 10.1016/j.tibs.2010.03.002 20399103; PubMed Central PMCID: PMC3131691.

60. Swingle M, Ni L, Honkanen RE. Small-molecule inhibitors of ser/thr protein phosphatases: specificity, use and common forms of abuse. Methods Mol Biol. 2007;365:23–38. Epub 2007/01/04. doi: 10.1385/1-59745-267-X:23 17200551; PubMed Central PMCID: PMC2709456.

61. Ishihara H, Martin BL, Brautigan DL, Karaki H, Ozaki H, Kato Y, et al. Calyculin A and okadaic acid: inhibitors of protein phosphatase activity. Biochem Biophys Res Commun. 1989;159(3):871–7. Epub 1989/03/31. doi: 10.1016/0006-291x(89)92189-x 2539153.

62. Hiraga S, Alvino GM, Chang F, Lian HY, Sridhar A, Kubota T, et al. Rif1 controls DNA replication by directing Protein Phosphatase 1 to reverse Cdc7-mediated phosphorylation of the MCM complex. Genes Dev. 2014;28(4):372–83. Epub 2014/02/18. doi: 10.1101/gad.231258.113 24532715; PubMed Central PMCID: PMC3937515.

63. Nishitani H, Lygerou Z, Nishimoto T. Proteolysis of DNA replication licensing factor Cdt1 in S-phase is performed independently of geminin through its N-terminal region. J Biol Chem. 2004;279(29):30807–16. Epub 2004/05/13. doi: 10.1074/jbc.M312644200 15138268.

64. Agarwal S, Smith KP, Zhou Y, Suzuki A, McKenney RJ, Varma D. Cdt1 stabilizes kinetochore-microtubule attachments via an Aurora B kinase-dependent mechanism. J Cell Biol. 2018;217(10):3446–63. Epub 2018/08/30. doi: 10.1083/jcb.201705127 30154187; PubMed Central PMCID: PMC6168275.

65. Koivomagi M, Valk E, Venta R, Iofik A, Lepiku M, Balog ER, et al. Cascades of multisite phosphorylation control Sic1 destruction at the onset of S phase. Nature. 2011;480(7375):128–31. Epub 2011/10/14. doi: 10.1038/nature10560 21993622; PubMed Central PMCID: PMC3228899.

66. Geley S, Kramer E, Gieffers C, Gannon J, Peters JM, Hunt T. Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint. J Cell Biol. 2001;153(1):137–48. Epub 2001/04/04. doi: 10.1083/jcb.153.1.137 11285280; PubMed Central PMCID: PMC2185534.

67. den Elzen N, Pines J. Cyclin A is destroyed in prometaphase and can delay chromosome alignment and anaphase. J Cell Biol. 2001;153(1):121–36. Epub 2001/04/04. doi: 10.1083/jcb.153.1.121 11285279; PubMed Central PMCID: PMC2185531.

68. Frigola J, He J, Kinkelin K, Pye VE, Renault L, Douglas ME, et al. Cdt1 stabilizes an open MCM ring for helicase loading. Nat Commun. 2017;8:15720. doi: 10.1038/ncomms15720 28643783.

69. Yuan Z, Riera A, Bai L, Sun J, Nandi S, Spanos C, et al. Structural basis of Mcm2-7 replicative helicase loading by ORC-Cdc6 and Cdt1. Nat Struct Mol Biol. 2017. doi: 10.1038/nsmb.3372 28191893.

70. Zhai Y, Cheng E, Wu H, Li N, Yung PY, Gao N, et al. Open-ringed structure of the Cdt1-Mcm2-7 complex as a precursor of the MCM double hexamer. Nat Struct Mol Biol. 2017;24(3):300–8. doi: 10.1038/nsmb.3374 28191894.

71. Campos CBL, Bédard PA, Linden R. Activation of p38 mitogen-activated protein kinase during normal mitosis in the developing retina. Neuroscience. 2002;112(3):583–91. doi: 10.1016/s0306-4522(02)00096-9 12074900

72. Thornton TM, Rincon M. Non-classical p38 map kinase functions: cell cycle checkpoints and survival. Int J Biol Sci. 2009;5(1):44–51. Epub 2009/01/23. doi: 10.7150/ijbs.5.44 19159010; PubMed Central PMCID: PMC2610339.

73. Ticau S, Friedman LJ, Champasa K, Correa IR Jr., Gelles J, Bell SP. Mechanism and timing of Mcm2-7 ring closure during DNA replication origin licensing. Nat Struct Mol Biol. 2017;24(3):309–15. Epub 2017/02/14. doi: 10.1038/nsmb.3375 28191892; PubMed Central PMCID: PMC5336523.

74. Hossain M, Bhalla K, Stillman B. Cyclin binding Cy motifs have multiple activities in the initiation of DNA replication. bioRxiv. 2019:681668. doi: 10.1101/681668

75. Wakula P, Beullens M, Ceulemans H, Stalmans W, Bollen M. Degeneracy and function of the ubiquitous RVXF motif that mediates binding to protein phosphatase-1. J Biol Chem. 2003;278(21):18817–23. Epub 2003/03/27. doi: 10.1074/jbc.M300175200 12657641.

76. Alver RC, Chadha GS, Gillespie PJ, Blow JJ. Reversal of DDK-Mediated MCM Phosphorylation by Rif1-PP1 Regulates Replication Initiation and Replisome Stability Independently of ATR/Chk1. Cell Rep. 2017;18(10):2508–20. Epub 2017/03/09. doi: 10.1016/j.celrep.2017.02.042 28273463; PubMed Central PMCID: PMC5357733.

77. Hiraga SI, Ly T, Garzon J, Horejsi Z, Ohkubo YN, Endo A, et al. Human RIF1 and protein phosphatase 1 stimulate DNA replication origin licensing but suppress origin activation. EMBO Rep. 2017;18(3):403–19. Epub 2017/01/13. doi: 10.15252/embr.201641983 28077461; PubMed Central PMCID: PMC5331243.

78. Arias EE, Walter JC. PCNA functions as a molecular platform to trigger Cdt1 destruction and prevent re-replication. Nat Cell Biol. 2006;8(1):84–90. doi: 10.1038/ncb1346 16362051.

79. Nguyen VQ, Co C, Li JJ. Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature. 2001;411(6841):1068–73. Epub 2001/06/29. doi: 10.1038/35082600 11429609.

80. Tardat M, Brustel J, Kirsh O, Lefevbre C, Callanan M, Sardet C, et al. The histone H4 Lys 20 methyltransferase PR-Set7 regulates replication origins in mammalian cells. Nat Cell Biol. 2010;12(11):1086–93. Epub 2010/10/19. doi: 10.1038/ncb2113 20953199.

81. Malecki MJ, Sanchez-Irizarry C, Mitchell JL, Histen G, Xu ML, Aster JC, et al. Leukemia-associated mutations within the NOTCH1 heterodimerization domain fall into at least two distinct mechanistic classes. Mol Cell Biol. 2006;26(12):4642–51. doi: 10.1128/MCB.01655-05 16738328; PubMed Central PMCID: PMC1489116.

82. White AE, Burch BD, Yang XC, Gasdaska PY, Dominski Z, Marzluff WF, et al. Drosophila histone locus bodies form by hierarchical recruitment of components. J Cell Biol. 2011;193(4):677–94. Epub 2011/05/18. doi: 10.1083/jcb.201012077 21576393; PubMed Central PMCID: PMC3166876.

83. Stokoe D, Campbell DG, Nakielny S, Hidaka H, Leevers SJ, Marshall C, et al. MAPKAP kinase-2; a novel protein kinase activated by mitogen-activated protein kinase. The EMBO journal. 1992;11(11):3985–94. Epub 1992/11/01. 1327754; PubMed Central PMCID: PMC556909.

84. Miller W, Rosenbloom K, Hardison RC, Hou M, Taylor J, Raney B, et al. 28-way vertebrate alignment and conservation track in the UCSC Genome Browser. Genome Res. 2007;17(12):1797–808. Epub 2007/11/07. doi: 10.1101/gr.6761107 17984227; PubMed Central PMCID: PMC2099589.


Článek vyšel v časopise

PLOS Genetics


2020 Číslo 8
Nejčtenější tento týden
Nejčtenější v tomto čísle
Kurzy

Zvyšte si kvalifikaci online z pohodlí domova

Hypertenze a hypercholesterolémie – synergický efekt léčby
nový kurz
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

Úloha kombinovaných preparátů v léčbě arteriální hypertenze
Autoři: prof. MUDr. Martin Haluzík, DrSc.

Halitóza
Autoři: MUDr. Ladislav Korábek, CSc., MBA

Terapie roztroušené sklerózy v kostce
Autoři: MUDr. Dominika Šťastná, Ph.D.

Všechny kurzy
Přihlášení
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.

Přihlášení

Nemáte účet?  Registrujte se

#ADS_BOTTOM_SCRIPTS#