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Cell Cycle Progression and Synchronization: An Overview

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Cell-Cycle Synchronization

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2579))

Abstract

The cell cycle is the series of events that take place in a cell that drives it to divide and produce two new daughter cells. Through more than 100 years of efforts by scientists, we now have a much clearer picture of cell cycle progression and its regulation. The typical cell cycle in eukaryotes is composed of the G1, S, G2, and M phases. The M phase is further divided into prophase, prometaphase, metaphase, anaphase, telophase, and cytokinesis. Cell cycle progression is mediated by cyclin-dependent kinases (Cdks) and their regulatory cyclin subunits. However, the driving force of cell cycle progression is growth factor-initiated signaling pathways that controls the activity of various Cdk-cyclin complexes. Most cellular events, including DNA duplication, gene transcription, protein translation, and post-translational modification of proteins, occur in a cell-cycle-dependent manner. To understand these cellular events and their underlying molecular mechanisms, it is desirable to have a population of cells that are traversing the cell cycle synchronously. This can be achieved through a process called cell synchronization. Many methods have been developed to synchronize cells to the various phases of the cell cycle. These methods could be classified into two groups: synchronization methods using chemical inhibitors and synchronization methods without using chemical inhibitors. All these methods have their own merits and shortcomings.

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References

  1. Wolpert L (1995) Evolution of the cell theory. Philos Trans R Soc Lond Ser B Biol Sci 349(1329):227–233

    Article  CAS  Google Scholar 

  2. Müller-Wille S (2010) Cell theory, specificity, and reproduction, 1837–1870. Stud Hist Phil Biol Biomed Sci 41(3):225–231

    Article  Google Scholar 

  3. Ribatti D (2019) Rudolf Virchow, the founder of cellular pathology. Rom J Morphol Embryol = Revue Roumaine de Morphologie et Embryologie 60(4):1381–1382

    Google Scholar 

  4. Wang Z (2021) Regulation of cell cycle progression by growth factor-induced cell signaling. Cell 10(12):3327

    Article  CAS  Google Scholar 

  5. Panagopoulos A, Altmeyer M (2021) The hammer and the dance of cell cycle control. Trends Biochem Sci 46(4):301–314

    Article  CAS  PubMed  Google Scholar 

  6. Barnum KJ, O’Connell MJ (2014) Cell cycle regulation by checkpoints. Methods Mol Biol 1170:29–40

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Satyanarayana A, Kaldis P (2009) Mammalian cell-cycle regulation: several Cdks, numerous cyclins and diverse compensatory mechanisms. Oncogene 28(33):2925–2939

    Article  CAS  PubMed  Google Scholar 

  8. Gao X, Leone GW, Wang H (2020) Cyclin D-CDK4/6 functions in cancer. Adv Cancer Res 148:147–169

    Article  CAS  PubMed  Google Scholar 

  9. Jones SM, Kazlauskas A (2000) Connecting signaling and cell cycle progression in growth factor-stimulated cells. Oncogene 19(49):5558–5567

    Article  CAS  PubMed  Google Scholar 

  10. Wee P, Wang Z (2017) Cell cycle synchronization of HeLa cells to assay EGFR pathway activation. Methods Mol Biol 1652:167–181

    Article  CAS  PubMed  Google Scholar 

  11. Davis PK, Ho A, Dowdy SF (2001) Biological methods for cell-cycle synchronization of mammalian cells. BioTechniques 30(6):1322. -1326, 1328, 1330-1321

    Article  CAS  PubMed  Google Scholar 

  12. Cooper S (2003) Rethinking synchronization of mammalian cells for cell cycle analysis. Cell Mol Life Sci 60(6):1099–1106

    Article  CAS  PubMed  Google Scholar 

  13. Banfalvi G (2017) Overview of cell synchronization. Methods Molecular Biol 1524:3–27

    Article  CAS  Google Scholar 

  14. Ligasová A, Koberna K (2021) Strengths and weaknesses of cell synchronization protocols based on inhibition of DNA synthesis. Int J Mol Sci 22(19):10759

    Google Scholar 

  15. Paweletz N (2001) Walther Flemming: pioneer of mitosis research. Nat Rev Mol Cell Biol 2(1):72–75

    Article  CAS  PubMed  Google Scholar 

  16. Howard A, Pelc SR (1951) Synthesis of nucleoprotein in bean root cells. Nature 167(4250):599–600

    Article  CAS  PubMed  Google Scholar 

  17. Rao PN, Johnson RT (1970) Mammalian cell fusion: studies on the regulation of DNA synthesis and mitosis. Nature 225(5228):159–164

    Article  CAS  PubMed  Google Scholar 

  18. Johnson RT, Rao PN (1971) Nucleo-cytoplasmic interactions in the acheivement of nuclear synchrony in DNA synthesis and mitosis in multinucleate cells. Biol Rev Camb Philos Soc 46(1):97–155

    Article  CAS  PubMed  Google Scholar 

  19. Hartwell LH, Culotti J, Reid B (1970) Genetic control of the cell-division cycle in yeast. I. Detection of mutants. Proc Natl Acad Sci U S A 66(2):352–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hartwell LH, Culotti J, Pringle JR, Reid BJ (1974) Genetic control of the cell division cycle in yeast. Science 183(4120):46–51

    Article  CAS  PubMed  Google Scholar 

  21. Hartwell LH (1991) Twenty-five years of cell cycle genetics. Genetics 129(4):975–980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Nurse P, Thuriaux P (1980) Regulatory genes controlling mitosis in the fission yeast Schizosaccharomyces pombe. Genetics 96(3):627–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lee MG, Nurse P (1987) Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature 327(6117):31–35

    Article  CAS  PubMed  Google Scholar 

  24. Lee MG, Norbury CJ, Spurr NK, Nurse P (1988) Regulated expression and phosphorylation of a possible mammalian cell-cycle control protein. Nature 333(6174):676–679

    Article  CAS  PubMed  Google Scholar 

  25. Evans T, Rosenthal ET, Youngblom J, Distel D, Hunt T (1983) Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell 33(2):389–396

    Article  CAS  PubMed  Google Scholar 

  26. Pryor PR, Jackson L, Gray SR, Edeling MA, Thompson A, Sanderson CM, Evans PR, Owen DJ, Luzio JP (2008) Molecular basis for the sorting of the SNARE VAMP7 into endocytic clathrin-coated vesicles by the ArfGAP Hrb. Cell 134(5):817–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Bashir T, Pagano M (2005) Cdk1: the dominant sibling of Cdk2. Nat Cell Biol 7(8):779–781

    Article  CAS  PubMed  Google Scholar 

  28. Weinert TA, Hartwell LH (1988) The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae. Science 241(4863):317–322

    Article  CAS  PubMed  Google Scholar 

  29. Hartwell LH, Weinert TA (1989) Checkpoints: controls that ensure the order of cell cycle events. Science 246(4930):629–634

    Article  CAS  PubMed  Google Scholar 

  30. Morgan DO (1997) Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu Rev Cell Dev Biol 13:261–291

    Article  CAS  PubMed  Google Scholar 

  31. Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13(12):1501–1512

    Article  CAS  PubMed  Google Scholar 

  32. Sherr CJ, Roberts JM (2004) Living with or without cyclins and cyclin-dependent kinases. Genes Dev 18(22):2699–2711

    Article  CAS  PubMed  Google Scholar 

  33. Weinberg RA (1995) The retinoblastoma protein and cell cycle control. Cell 81(3):323–330

    Article  CAS  PubMed  Google Scholar 

  34. Dyson N (1998) The regulation of E2F by pRB-family proteins. Genes Dev 12(15):2245–2262

    Article  CAS  PubMed  Google Scholar 

  35. Lundberg AS, Weinberg RA (1998) Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol 18(2):753–761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Petersen BO, Lukas J, Sørensen CS, Bartek J, Helin K (1999) Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization. EMBO J 18(2):396–410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Coverley D, Pelizon C, Trewick S, Laskey RA (2000) Chromatin-bound Cdc6 persists in S and G2 phases in human cells, while soluble Cdc6 is destroyed in a cyclin A-cdk2 dependent process. J Cell Sci 113(Pt 11):1929–1938

    Article  CAS  PubMed  Google Scholar 

  38. Riabowol K, Draetta G, Brizuela L, Vandre D, Beach D (1989) The cdc2 kinase is a nuclear protein that is essential for mitosis in mammalian cells. Cell 57(3):393–401

    Article  CAS  PubMed  Google Scholar 

  39. Duan L, Raja SM, Chen G, Virmani S, Williams SH, Clubb RJ, Mukhopadhyay C, Rainey MA, Ying G, Dimri M et al (2011) Negative regulation of EGFR-Vav2 signaling axis by Cbl ubiquitin ligase controls EGF receptor-mediated epithelial cell adherens junction dynamics and cell migration. J Biol Chem 286(1):620–633

    Article  CAS  PubMed  Google Scholar 

  40. Limas JC, Cook JG (2019) Preparation for DNA replication: the key to a successful S phase. FEBS Lett 593(20):2853–2867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Massague J (2004) G1 cell-cycle control and cancer. Nature 432(7015):298–306

    Article  CAS  PubMed  Google Scholar 

  42. Nelson DM, Ye X, Hall C, Santos H, Ma T, Kao GD, Yen TJ, Harper JW, Adams PD (2002) Coupling of DNA synthesis and histone synthesis in S phase independent of cyclin/cdk2 activity. Mol Cell Biol 22(21):7459–7472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ciardo D, Goldar A, Marheineke K (2019) On the interplay of the DNA replication program and the intra-S phase checkpoint pathway. Genes 10(2):94

    Google Scholar 

  44. Saldivar JC, Hamperl S, Bocek MJ, Chung M, Bass TE, Cisneros-Soberanis F, Samejima K, Xie L, Paulson JR, Earnshaw WC et al (2018) An intrinsic S/G(2) checkpoint enforced by ATR. Science 361(6404):806–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hannen R, Selmansberger M, Hauswald M, Pagenstecher A, Nist A, Stiewe T, Acker T, Carl B, Nimsky C, Bartsch JW (2019) Comparative transcriptomic analysis of temozolomide resistant primary GBM stem-like cells and recurrent GBM identifies up-regulation of the carbonic anhydrase CA2 gene as resistance factor. Cancers 11(7):921

    Article  CAS  PubMed Central  Google Scholar 

  46. Lockhead S, Moskaleva A, Kamenz J, Chen Y, Kang M, Reddy AR, Santos SDM, Ferrell JE Jr (2020) The apparent requirement for protein synthesis during G2 phase is due to checkpoint activation. Cell Rep 32(2):107901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Moseley JB, Mayeux A, Paoletti A, Nurse P (2009) A spatial gradient coordinates cell size and mitotic entry in fission yeast. Nature 459(7248):857–860

    Article  CAS  PubMed  Google Scholar 

  48. Burgoyne PS, Mahadevaiah SK, Turner JM (2007) The management of DNA double-strand breaks in mitotic G2, and in mammalian meiosis viewed from a mitotic G2 perspective. Bioessays 29(10):974–986

    Article  CAS  PubMed  Google Scholar 

  49. Zahnreich S, Weber B, Rösch G, Schindler D, Schmidberger H (2020) Compromised repair of radiation-induced DNA double-strand breaks in Fanconi anemia fibroblasts in G2. DNA Repair 96:102992

    Article  CAS  PubMed  Google Scholar 

  50. Gibcus JH, Samejima K, Goloborodko A, Samejima I, Naumova N, Nuebler J, Kanemaki MT, Xie L, Paulson JR, Earnshaw WC et al (2018) A pathway for mitotic chromosome formation. Science 359(6376):eaao6135

    Google Scholar 

  51. Liang Z, Zickler D, Prentiss M, Chang FS, Witz G, Maeshima K, Kleckner N (2015) Chromosomes progress to metaphase in multiple discrete steps via global compaction/expansion cycles. Cell 161(5):1124–1137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Samejima K, Samejima I, Vagnarelli P, Ogawa H, Vargiu G, Kelly DA, de Lima AF, Kerr A, Green LC, Hudson DF et al (2012) Mitotic chromosomes are compacted laterally by KIF4 and condensin and axially by topoisomerase IIα. J Cell Biol 199(5):755–770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Gavet O, Pines J (2010) Progressive activation of CyclinB1-Cdk1 coordinates entry to mitosis. Dev Cell 18(4):533–543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Santaguida S, Musacchio A (2009) The life and miracles of kinetochores. EMBO J 28(17):2511–2531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Vukušić K, Tolić IM (2021) Anaphase B: long-standing models meet new concepts. Semin Cell Dev Biol 117:127–139

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Su KC, Barry Z, Schweizer N, Maiato H, Bathe M, Cheeseman IM (2016) A regulatory switch alters chromosome motions at the metaphase-to-anaphase transition. Cell Rep 17(7):1728–1738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Vukušić K, Buđa R, Tolić IM (2019) Force-generating mechanisms of anaphase in human cells. J Cell Sci 132(18):jcs231485

    Google Scholar 

  58. Afonso O, Matos I, Pereira AJ, Aguiar P, Lampson MA, Maiato H (2014) Feedback control of chromosome separation by a midzone Aurora B gradient. Science 345(6194):332–336

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Green RA, Paluch E, Oegema K (2012) Cytokinesis in animal cells. Annu Rev Cell Dev Biol 28:29–58

    Article  CAS  PubMed  Google Scholar 

  60. Fededa JP, Gerlich DW (2012) Molecular control of animal cell cytokinesis. Nat Cell Biol 14(5):440–447

    Article  CAS  PubMed  Google Scholar 

  61. Lens SMA, Medema RH (2019) Cytokinesis defects and cancer. Nat Rev Cancer 19(1):32–45

    Article  CAS  PubMed  Google Scholar 

  62. Mierzwa B, Gerlich DW (2014) Cytokinetic abscission: molecular mechanisms and temporal control. Dev Cell 31(5):525–538

    Article  CAS  PubMed  Google Scholar 

  63. Gromley A, Yeaman C, Rosa J, Redick S, Chen CT, Mirabelle S, Guha M, Sillibourne J, Doxsey SJ (2005) Centriolin anchoring of exocyst and SNARE complexes at the midbody is required for secretory-vesicle-mediated abscission. Cell 123(1):75–87

    Article  CAS  PubMed  Google Scholar 

  64. Schiel JA, Park K, Morphew MK, Reid E, Hoenger A, Prekeris R (2011) Endocytic membrane fusion and buckling-induced microtubule severing mediate cell abscission. J Cell Sci 124(Pt 9):1411–1424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Jones SM, Kazlauskas A (2001) Growth-factor-dependent mitogenesis requires two distinct phases of signalling. Nat Cell Biol 3(2):165–172

    Article  CAS  PubMed  Google Scholar 

  66. Murphy JS, D’Alisa R, Gershey EL, Landsberger FR (1978) Kinetics of desynchronization and distribution of generation times in synchronized cell populations. Proc Natl Acad Sci U S A 75(9):4404–4407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Polyak K, Kato JY, Solomon MJ, Sherr CJ, Massague J, Roberts JM, Koff A (1994) p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes Dev 8(1):9–22

    Article  CAS  PubMed  Google Scholar 

  68. Chen D, Walsh K, Wang J (2000) Regulation of cdk2 activity in endothelial cells that are inhibited from growth by cell contact. Arterioscler Thromb Vasc Biol 20(3):629–635

    Article  CAS  PubMed  Google Scholar 

  69. Leontieva OV, Demidenko ZN, Blagosklonny MV (2014) Contact inhibition and high cell density deactivate the mammalian target of rapamycin pathway, thus suppressing the senescence program. Proc Natl Acad Sci U S A 111(24):8832–8837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Abercrombie M (1979) Contact inhibition and malignancy. Nature 281(5729):259–262

    Article  CAS  PubMed  Google Scholar 

  71. Zwanenburg TS (1983) Standardized shake-off to synchronize cultured CHO cells. Mutat Res 120(2–3):151–159

    Article  CAS  PubMed  Google Scholar 

  72. Cao G, Liu LM, Cleary SF (1991) Modified method of mammalian cell synchronization improves yield and degree of synchronization. Exp Cell Res 193(2):405–410

    Article  CAS  PubMed  Google Scholar 

  73. Hulleman E, Bijvelt JJ, Verkleij AJ, Verrips CT, Boonstra J (1999) Integrin signaling at the M/G1 transition induces expression of cyclin E. Exp Cell Res 253(2):422–431

    Article  CAS  PubMed  Google Scholar 

  74. Wee P, Shi H, Jiang J, Wang Y, Wang Z (2015) EGF stimulates the activation of EGF receptors and the selective activation of major signaling pathways during mitosis. Cell Signal 27(3):638–651

    Article  CAS  PubMed  Google Scholar 

  75. Vecsler M, Lazar I, Tzur A (2013) Using standard optical flow cytometry for synchronizing proliferating cells in the G1 phase. PLoS One 8(12):e83935

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Juan G, Hernando E, Cordon-Cardo C (2002) Separation of live cells in different phases of the cell cycle for gene expression analysis. Cytometry 49(4):170–175

    Article  PubMed  Google Scholar 

  77. Banfalvi G (2008) Cell cycle synchronization of animal cells and nuclei by centrifugal elutriation. Nat Protoc 3(4):663–673

    Article  CAS  PubMed  Google Scholar 

  78. Liu Y, Nan B, Niu J, Kapler GM, Gao S (2021) An optimized and versatile counter-flow centrifugal elutriation workflow to obtain synchronized eukaryotic cells. Front Cell Dev Biol 9:664418

    Article  PubMed  PubMed Central  Google Scholar 

  79. Hengstschläger M, Knöfler M, Müllner EW, Ogris E, Wintersberger E, Wawra E (1994) Different regulation of thymidine kinase during the cell cycle of normal versus DNA tumor virus-transformed cells. J Biol Chem 269(19):13836–13842

    Article  PubMed  Google Scholar 

  80. Hengstschläger M, Pusch O, Soucek T, Hengstschläger-Ottnad E, Bernaschek G (1997) Quality control of centrifugal elutriation for studies of cell cycle regulations. BioTechniques 23(2):232–234. 236-237

    Article  PubMed  Google Scholar 

  81. Vaughn JP, Cirisano FD, Huper G, Berchuck A, Futreal PA, Marks JR, Iglehart JD (1996) Cell cycle control of BRCA2. Cancer Res 56(20):4590–4594

    CAS  PubMed  Google Scholar 

  82. Zurbriggen R, Dreyer JL (1996) The plasma membrane NADH-diaphorase is active during selective phases of the cell cycle in mouse neuroblastoma cell line NB41A3. Its relation to cell growth and differentiation. Biochim Biophys Acta 1312(3):215–222

    Article  PubMed  Google Scholar 

  83. Ly T, Endo A, Lamond AI (2015) Proteomic analysis of the response to cell cycle arrests in human myeloid leukemia cells. eLife 4:e04534

    Google Scholar 

  84. Lissy NA, Van Dyk LF, Becker-Hapak M, Vocero-Akbani A, Mendler JH, Dowdy SF (1998) TCR antigen-induced cell death occurs from a late G1 phase cell cycle check point. Immunity 8(1):57–65

    Article  CAS  PubMed  Google Scholar 

  85. Kim HD, Tomida A, Ogiso Y, Tsuruo T (1999) Glucose-regulated stresses cause degradation of DNA topoisomerase IIalpha by inducing nuclear proteasome during G1 cell cycle arrest in cancer cells. J Cell Physiol 180(1):97–104

    Article  CAS  PubMed  Google Scholar 

  86. Méndez J, Stillman B (2000) Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis. Mol Cell Biol 20(22):8602–8612

    Article  PubMed  PubMed Central  Google Scholar 

  87. Willis N, Rhind N (2011) Studying G2 DNA damage checkpoints using the fission yeast Schizosaccharomyces pombe. Methods Mol Biol 782:1–12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hagan IM, Grallert A, Simanis V (2016) Cell cycle synchronization of schizosaccharomyces pombe by centrifugal elutriation of small cells. Cold Spring Harb Protoc 2016(6):508–515

    Google Scholar 

  89. Rosebrock AP (2017) Synchronization of budding yeast by centrifugal elutriation. Cold Spring Harb Protoc 2017(1):53–62

    Google Scholar 

  90. Horlock-Roberts K, Reaume C, Dayer G, Ouellet C, Cook N, Yee J (2017) Drug-free approach to study the unusual cell cycle of giardia intestinalis. mSphere 2(5):e00384–16

    Google Scholar 

  91. Crozier TWM, Tinti M, Wheeler RJ, Ly T, Ferguson MAJ, Lamond AI (2018) Proteomic analysis of the cell cycle of procylic form Trypanosoma brucei. Mol Cell Proteomics 17(6):1184–1195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Keyomarsi K, Sandoval L, Band V, Pardee AB (1991) Synchronization of tumor and normal cells from G1 to multiple cell cycles by lovastatin. Cancer Res 51(13):3602–3609

    CAS  PubMed  Google Scholar 

  93. Javanmoghadam-Kamrani S, Keyomarsi K (2008) Synchronization of the cell cycle using lovastatin. Cell Cycle 7(15):2434–2440

    Article  CAS  PubMed  Google Scholar 

  94. Lee SJ, Ha MJ, Lee J, Nguyen P, Choi YH, Pirnia F, Kang WK, Wang XF, Kim SJ, Trepel JB (1998) Inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme a reductase pathway induces p53-independent transcriptional regulation of p21(WAF1/CIP1) in human prostate carcinoma cells. J Biol Chem 273(17):10618–10623

    Article  CAS  PubMed  Google Scholar 

  95. Bjursell G, Reichard P (1973) Effects of thymidine on deoxyribonucleoside triphosphate pools and deoxyribonucleic acid synthesis in Chinese hamster ovary cells. J Biol Chem 248(11):3904–3909

    Article  CAS  PubMed  Google Scholar 

  96. Schvartzman JB, Krimer DB, Van’t Hof J (1984) The effects of different thymidine concentrations on DNA replication in pea-root cells synchronized by a protracted 5-fluorodeoxyuridine treatment. Exp Cell Res 150(2):379–389

    Article  CAS  PubMed  Google Scholar 

  97. Singh A, Xu YJ (2016) The cell killing mechanisms of hydroxyurea. Genes 7(11):99

    Google Scholar 

  98. Vassilev LT (2006) Cell cycle synchronization at the G2/M phase border by reversible inhibition of CDK1. Cell Cycle 5(22):2555–2556

    Article  CAS  PubMed  Google Scholar 

  99. Vassilev LT, Tovar C, Chen S, Knezevic D, Zhao X, Sun H, Heimbrook DC, Chen L (2006) Selective small-molecule inhibitor reveals critical mitotic functions of human CDK1. Proc Natl Acad Sci U S A 103(28):10660–10665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Ma HT, Tsang YH, Marxer M, Poon RY (2009) Cyclin A2-cyclin-dependent kinase 2 cooperates with the PLK1-SCFbeta-TrCP1-EMI1-anaphase-promoting complex/cyclosome axis to promote genome reduplication in the absence of mitosis. Mol Cell Biol 29(24):6500–6514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Whittaker SR, Walton MI, Garrett MD, Workman P (2004) The cyclin-dependent kinase inhibitor CYC202 (R-roscovitine) inhibits retinoblastoma protein phosphorylation, causes loss of cyclin D1, and activates the mitogen-activated protein kinase pathway. Cancer Res 64(1):262–272

    Article  CAS  PubMed  Google Scholar 

  102. Chan KS, Koh CG, Li HY (2012) Mitosis-targeted anti-cancer therapies: where they stand. Cell Death Dis 3:e411

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Lara-Gonzalez P, Westhorpe FG, Taylor SS (2012) The spindle assembly checkpoint. Curr Biol 22(22):R966–R980

    Article  CAS  PubMed  Google Scholar 

  104. Zieve GW, Turnbull D, Mullins JM, McIntosh JR (1980) Production of large numbers of mitotic mammalian cells by use of the reversible microtubule inhibitor nocodazole. Nocodazole accumulated mitotic cells. Exp Cell Res 126(2):397–405

    Article  CAS  PubMed  Google Scholar 

  105. Blagosklonny MV (2007) Mitotic arrest and cell fate: why and how mitotic inhibition of transcription drives mutually exclusive events. Cell Cycle 6(1):70–74

    Article  CAS  PubMed  Google Scholar 

  106. Lee DH, Goldberg AL (1998) Proteasome inhibitors: valuable new tools for cell biologists. Trends Cell Biol 8(10):397–403

    Article  CAS  PubMed  Google Scholar 

  107. Dulla K, Daub H, Hornberger R, Nigg EA, Korner R (2010) Quantitative site-specific phosphorylation dynamics of human protein kinases during mitotic progression. Mol Cell Proteomics 9(6):1167–1181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Li R, Murray AW (1991) Feedback control of mitosis in budding yeast. Cell 66(3):519–531

    Article  CAS  PubMed  Google Scholar 

  109. Holloway SL, Glotzer M, King RW, Murray AW (1993) Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor. Cell 73(7):1393–1402

    Article  CAS  PubMed  Google Scholar 

  110. Hornig NC, Knowles PP, McDonald NQ, Uhlmann F (2002) The dual mechanism of separase regulation by securin. Curr Biol 12(12):973–982

    Article  CAS  PubMed  Google Scholar 

  111. Waizenegger I, Giménez-Abián JF, Wernic D, Peters JM (2002) Regulation of human separase by securin binding and autocleavage. Curr Biol 12(16):1368–1378

    Article  CAS  PubMed  Google Scholar 

  112. Josefsberg LB, Galiani D, Dantes A, Amsterdam A, Dekel N (2000) The proteasome is involved in the first metaphase-to-anaphase transition of meiosis in rat oocytes. Biol Reprod 62(5):1270–1277

    Article  CAS  PubMed  Google Scholar 

  113. Matsui Y, Nakayama Y, Okamoto M, Fukumoto Y, Yamaguchi N (2012) Enrichment of cell populations in metaphase, anaphase, and telophase by synchronization using nocodazole and blebbistatin: a novel method suitable for examining dynamic changes in proteins during mitotic progression. Eur J Cell Biol 91(5):413–419

    Article  CAS  PubMed  Google Scholar 

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Wang, Z. (2022). Cell Cycle Progression and Synchronization: An Overview. In: Wang, Z. (eds) Cell-Cycle Synchronization. Methods in Molecular Biology, vol 2579. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2736-5_1

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