1932

Abstract

The most fundamental feature of cellular form is size, which sets the scale of all cell biological processes. Growth, form, and function are all necessarily linked in cell biology, but we often do not understand the underlying molecular mechanisms nor their specific functions. Here, we review progress toward determining the molecular mechanisms that regulate cell size in yeast, animals, and plants, as well as progress toward understanding the function of cell size regulation. It has become increasingly clear that the mechanism of cell size regulation is deeply intertwined with basic mechanisms of biosynthesis, and how biosynthesis can be scaled (or not) in proportion to cell size. Finally, we highlight recent findings causally linking aberrant cell size regulation to cellular senescence and their implications for cancer therapies.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cellbio-120219-040142
2022-10-06
2024-06-14
Loading full text...

Full text loading...

/deliver/fulltext/cellbio/38/1/annurev-cellbio-120219-040142.html?itemId=/content/journals/10.1146/annurev-cellbio-120219-040142&mimeType=html&fmt=ahah

Literature Cited

  1. Allard CAH, Opalko HE, Liu K-W, Medoh U, Moseley JB. 2018. Cell size–dependent regulation of Wee1 localization by Cdr2 cortical nodes. J. Cell Biol. 217:51589–99
    [Google Scholar]
  2. Baptista T, Grünberg S, Minoungou N, Koster MJE, Timmers HTM et al. 2017. SAGA is a general cofactor for RNA polymerase II transcription. Mol. Cell 68:1130–43.e5
    [Google Scholar]
  3. Barber F, Amir A, Murray AW. 2020. Cell-size regulation in budding yeast does not depend on linear accumulation of Whi5. PNAS 117:2514243–50
    [Google Scholar]
  4. Bastajian N, Friesen H, Andrews BJ. 2013. Bck2 acts through the MADS box protein Mcm1 to activate cell-cycle-regulated genes in budding yeast. PLOS Genet. 9:5e1003507
    [Google Scholar]
  5. Battich N, Stoeger T, Pelkmans L. 2015. Control of transcript variability in single mammalian cells. Cell 163:71596–610
    [Google Scholar]
  6. Berry S, Müller M, Pelkmans L. 2021. Nuclear RNA concentration coordinates RNA production with cell size in human cells. bioRxiv 444432. https://doi.org/10.1101/2021.05.17.444432
    [Crossref]
  7. Biran A, Zada L, Abou Karam P, Vadai E, Roitman L et al. 2017. Quantitative identification of senescent cells in aging and disease. Aging Cell 16:4661–71
    [Google Scholar]
  8. Cadart C, Monnier S, Grilli J, Sáez PJ, Srivastava N et al. 2018. Size control in mammalian cells involves modulation of both growth rate and cell cycle duration. Nat. Commun. 9:3275
    [Google Scholar]
  9. Cadart C, Piel M, Lagomarsino MC. 2021. Volume growth in animal cells is cell cycle dependent and shows additive fluctuations. bioRxiv 446986. https://doi.org/10.1101/2021.06.03.446986
    [Crossref]
  10. Cadart C, Venkova L, Recho P, Lagomarsino MC, Piel M. 2019. The physics of cell-size regulation across timescales. Nat. Phys. 15:10993–1004
    [Google Scholar]
  11. Cadart C, Zlotek-Zlotkiewicz E, Venkova L, Thouvenin O, Racine V et al. 2017. Fluorescence eXclusion Measurement of volume in live cells. Methods Cell Biol. 139:103–20
    [Google Scholar]
  12. Campisi J, Kapahi P, Lithgow GJ, Melov S, Newman JC, Verdin E. 2019. From discoveries in ageing research to therapeutics for healthy ageing. Nature 571:7764183–92
    [Google Scholar]
  13. Campos M, Surovtsev IV, Kato S, Paintdakhi A, Beltran B et al. 2014. A constant size extension drives bacterial cell size homeostasis. Cell 159:61433–46
    [Google Scholar]
  14. Chandler-Brown D, Schmoller KM, Winetraub Y, Skotheim JM. 2017. The adder phenomenon emerges from independent control of pre- and post-start phases of the budding yeast cell cycle. Curr. Biol. 27:182774–83.e3
    [Google Scholar]
  15. Charvin G, Oikonomou C, Siggia ED, Cross FR. 2010. Origin of irreversibility of cell cycle start in budding yeast. PLOS Biol. 8:1e1000284
    [Google Scholar]
  16. Chen Y, Zhao G, Zahumensky J, Honey S, Futcher B 2020. Differential scaling of gene expression with cell size may explain size control in budding yeast. Mol. Cell 78:2359–70.e6
    [Google Scholar]
  17. Cheng L, Chen J, Kong Y, Tan C, Kafri R, Björklund M. 2021. Size-scaling promotes senescence-like changes in proteome and organelle content. bioRxiv 455193. https://doi.org/10.1101/2021.08.05.455193
    [Crossref]
  18. Childs BG, Durik M, Baker DJ, van Deursen JM. 2015. Cellular senescence in aging and age-related disease: from mechanisms to therapy. Nat. Med. 21:121424–35
    [Google Scholar]
  19. Claude K-L, Bureik D, Chatzitheodoridou D, Adarska P, Singh A, Schmoller KM 2021. Transcription coordinates histone amounts and genome content. Nature 12:4202
    [Google Scholar]
  20. Cockcroff C, den Boer BGW, Healy JMS, Murray JAH. 2000. Cyclin D control of growth rate in plants. Nature 405:575–79
    [Google Scholar]
  21. Conlon I, Raff M. 2003. Differences in the way a mammalian cell and yeast cells coordinate cell growth and cell-cycle progression. J. Biol. 2:7
    [Google Scholar]
  22. Costanzo M, Nishikawa JL, Tang X, Millman JS, Schub O et al. 2004. CDK activity antagonizes Whi5, an inhibitor of G1/S transcription in yeast. Cell 117:7899–913
    [Google Scholar]
  23. Crane MM, Tsuchiya M, Blue BW, Almazan JD, Chen KL et al. 2019. Rb analog Whi5 regulates G1 to S transition and cell size but not replicative lifespan in budding yeast. Translat. Med. Aging 3:104–8
    [Google Scholar]
  24. Creanor J, Mitchison JM. 1982. Patterns of protein synthesis during the cell cycle of the fission yeast Schizosaccharomyces pombe. J. Cell Sci. 58:263–85
    [Google Scholar]
  25. Cross FR. 1988. DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae. Mol. Cell. Biol. 8:114675–84
    [Google Scholar]
  26. Cross FR. 2020. Regulation of multiple fission and cell-cycle-dependent gene expression by CDKA1 and the Rb-E2F pathway in Chlamydomonas. Curr. Biol. 30:101855–65.e4
    [Google Scholar]
  27. Cross FR, Umen JG. 2015. The Chlamydomonas cell cycle. Plant J. 82:3370–92
    [Google Scholar]
  28. Crozier L, Foy R, Mouery BL, Whitaker RH, Corno A et al. 2021. CDK4/6 inhibitors induce replication stress to cause long-term cell cycle withdrawal. bioRxiv 428245. https://doi.org/10.1101/2021.02.03.428245
    [Crossref]
  29. Curran S, Dey G, Rees P, Nurse P. 2022. A quantitative and spatial analysis of cell cycle regulators during the fission yeast cycle. bioRxiv 488127. https://doi.org/10.1101/2022.04.13.488127
    [Crossref]
  30. Dannenberg JH, van Rossum A, Schuijff L, te Riele H. 2000. Ablation of the retinoblastoma gene family deregulates G1 control causing immortalization and increased cell turnover under growth-restricting conditions. Genes Dev. 14:233051–64
    [Google Scholar]
  31. D'Ario M, Tavares R, Schiessl K, Desvoyes B, Gutierrez C et al. 2021. Cell size controlled in plants using DNA content as an internal scale. Science 372:65471176–81
    [Google Scholar]
  32. de Bruin RAM, McDonald WH, Kalashnikova TI, Yates J, Wittenberg C. 2004. Cln3 activates G1-specific transcription via phosphorylation of the SBF bound repressor Whi5. Cell 117:7887–98
    [Google Scholar]
  33. Demidenko ZN, Blagosklonny MV. 2008. Growth stimulation leads to cellular senescence when the cell cycle is blocked. Cell Cycle 7:213355–61
    [Google Scholar]
  34. Demidenko ZN, Zubova SG, Bukreeva EI, Pospelov VA, Pospelova TV, Blagosklonny MV. 2009. Rapamycin decelerates cellular senescence. Cell Cycle 8:121888–95
    [Google Scholar]
  35. Deng L, Kabeche R, Wang N, Wu J-Q, Moseley JB. 2014. Megadalton-node assembly by binding of Skb1 to the membrane anchor Slf1. Mol. Biol. Cell 25:172660–68
    [Google Scholar]
  36. Di Talia S, Skotheim JM, Bean JM, Siggia ED, Cross FR. 2007. The effects of molecular noise and size control on variability in the budding yeast cell cycle. Nature 448:7156947–51
    [Google Scholar]
  37. Dick FA, Rubin SM. 2013. Molecular mechanisms underlying RB protein function. Nat. Rev. Mol. Cell Biol. 14:5297–306
    [Google Scholar]
  38. Dolfi SC, Chan LL-Y, Qiu J, Tedeschi PM, Bertino JR et al. 2013. The metabolic demands of cancer cells are coupled to their size and protein synthesis rates. Cancer Metab 1:20
    [Google Scholar]
  39. Dorsey S, Tollis S, Cheng J, Black L, Notley S et al. 2018. G1/S transcription factor copy number is a growth-dependent determinant of cell cycle commitment in yeast. Cell Syst. 6:5539–54.e11
    [Google Scholar]
  40. Elliott SG. 1983. Coordination of growth with cell division: regulation of synthesis of RNA during the cell cycle of the fission yeast Schizosaccharomyces pombe. Mol. Gen. Genet. 192:1–2204–11
    [Google Scholar]
  41. Elliott SG, McLaughlin CS. 1979. Regulation of RNA synthesis in yeast. III. Synthesis during the cell cycle. Mol. Gen. Genet. 169:3237–43
    [Google Scholar]
  42. Elliott SG, Warner JR, McLaughlin CS. 1979. Synthesis of ribosomal proteins during the cell cycle of the yeast Saccharomyces cerevisiae. J. Bacteriol. 137:21048–50
    [Google Scholar]
  43. Epstein CB, Cross FR. 1994. Genes that can bypass the CLN requirement for Saccharomyces cerevisiae cell cycle START. Mol. Cell. Biol. 14:32041–47
    [Google Scholar]
  44. Facchetti G, Chang F, Howard M. 2017. Controlling cell size through sizer mechanisms. Curr. Opin. Syst. Biol. 5:86–92
    [Google Scholar]
  45. Facchetti G, Knapp B, Flor-Parra I, Chang F, Howard M 2019. Reprogramming Cdr2-dependent geometry-based cell size control in fission yeast. Curr. Biol. 29:2350–58.e4
    [Google Scholar]
  46. Fang S-C, de los Reyes C, Umen JG. 2006. Cell size checkpoint control by the retinoblastoma tumor suppressor pathway. PLOS Genet. 2:10e167
    [Google Scholar]
  47. Fantes PA. 1977. Control of cell size and cycle time in Schizosaccharomyces pombe. J. Cell Sci. 24:51–67
    [Google Scholar]
  48. Fantes PA, Grant WD, Pritchard RH, Sudbery PE, Wheals AE. 1975. The regulation of cell size and the control of mitosis. J. Theor. Biol. 50:1213–44
    [Google Scholar]
  49. Ferrell JE. 2021. Understanding Cell Signaling: Motifs, Recurring Themes, and the Theory of Nonlinear Dynamics Boca Raton, FL: Taylor & Francis
    [Google Scholar]
  50. Ferrezuelo F, Aldea M, Futcher B. 2009. Bck2 is a phase-independent activator of cell cycle-regulated genes in yeast. Cell Cycle 8:2239–52
    [Google Scholar]
  51. Fisher RP. 2019. Cdk7: a kinase at the core of transcription and in the crosshairs of cancer drug discovery. Transcription 10:247–56
    [Google Scholar]
  52. Fraser RS, Nurse P. 1978. Novel cell cycle control of RNA synthesis in yeast. Nature 271:5647726–30
    [Google Scholar]
  53. Fraser RS, Nurse P. 1979. Altered patterns of ribonucleic acid synthesis during the cell cycle: a mechanism compensating for variation in gene concentration. J. Cell Sci. 35:25–40
    [Google Scholar]
  54. Futcher B. 1996. Cyclins and the wiring of the yeast cell cycle. Yeast 12:161635–46
    [Google Scholar]
  55. Garmendia-Torres C, Tassy O, Matifas A, Molina N, Charvin G. 2018. Multiple inputs ensure yeast cell size homeostasis during cell cycle progression. eLife 7:e34025
    [Google Scholar]
  56. Gerganova V, Floderer C, Archetti A, Michon L, Carlini L et al. 2019. Multi-phosphorylation reaction and clustering tune Pom1 gradient mid-cell levels according to cell size. eLife 8:e45983
    [Google Scholar]
  57. Ginzberg MB, Chang N, D'Souza H, Patel N, Kafri R, Kirschner MW. 2018. Cell size sensing in animal cells coordinates anabolic growth rates and cell cycle progression to maintain cell size uniformity. eLife 7:e26957
    [Google Scholar]
  58. Ginzberg MB, Kafri R, Kirschner M. 2015. On being the right (cell) size. Science 348:62361245075
    [Google Scholar]
  59. Godin M, Delgado FF, Son S, Grover WH, Bryan AK et al. 2010. Using buoyant mass to measure the growth of single cells. Nat. Methods 7:5387–90
    [Google Scholar]
  60. Guo T, Luna A, Rajapakse VN, Koh CC, Wu Z et al. 2019. Quantitative proteome landscape of the NCI-60 cancer cell lines. iScience 21:664–80
    [Google Scholar]
  61. Haimovich G, Medina DA, Causse SZ, Garber M, Millán-Zambrano G et al. 2013. Gene expression is circular: factors for mRNA degradation also foster mRNA synthesis. Cell 153:51000–11
    [Google Scholar]
  62. Hartwell LH, Unger MW. 1977. Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division. J. Cell Biol. 75:2422–35
    [Google Scholar]
  63. Heldt FS, Tyson JJ, Cross FR, Novák B. 2020. A single light-responsive sizer can control multiple-fission cycles in Chlamydomonas. Curr. Biol. 30:4634–44.e7
    [Google Scholar]
  64. Helenius K, Yang Y, Tselykh TV, Pessa HKJ, Frilander MJ, Mäkelä TP. 2011. Requirement of TFIIH kinase subunit Mat1 for RNA Pol II C-terminal domain Ser5 phosphorylation, transcription and mRNA turnover. Nucleic Acids. Res. 39:125025–35
    [Google Scholar]
  65. Hernandez-Segura A, Nehme J, Demaria M. 2018. Hallmarks of cellular senescence. Trends Cell Biol. 28:6436–53
    [Google Scholar]
  66. Ho P-Y, Lin J, Amir A 2018. Modeling cell size regulation: from single-cell-level statistics to molecular mechanisms and population-level effects. Annu. Rev. Biophys. 47:251–71
    [Google Scholar]
  67. Inzé D, De Veylder L. 2006. Cell cycle regulation in plant development. Annu. Rev. Genet. 40:77–105
    [Google Scholar]
  68. Janssens GE, Veenhoff LM. 2016. The natural variation in lifespans of single yeast cells is related to variation in cell size, ribosomal protein, and division time. PLOS ONE 11:12e0167394
    [Google Scholar]
  69. Johnston GC, Pringle JR, Hartwell LH. 1977. Coordination of growth with cell division in the yeast Saccharomyces cerevisiae. Exp. Cell Res. 105:179–98
    [Google Scholar]
  70. Jones AR, Forero-Vargas M, Withers SP, Smith RS, Traas J et al. 2017. Cell-size dependent progression of the cell cycle creates homeostasis and flexibility of plant cell size. Nat. Commun. 8:15060
    [Google Scholar]
  71. Jorgensen P, Edgington NP, Schneider BL, Rupes I, Tyers M, Futcher B. 2007. The size of the nucleus increases as yeast cells grow. Mol. Biol. Cell 18:93523–32
    [Google Scholar]
  72. Jun S, Si F, Pugatch R, Scott M. 2018. Fundamental principles in bacterial physiology—history, recent progress, and the future with focus on cell size control: a review. Rep. Prog. Phys. 81:5056601
    [Google Scholar]
  73. Kaeberlein M. 2010. Lessons on longevity from budding yeast. Nature 464:7288513–19
    [Google Scholar]
  74. Keifenheim D, Sun X-M, D'Souza E, Ohira MJ, Magner M et al. 2017. Size-dependent expression of the mitotic activator Cdc25 suggests a mechanism of size control in fission yeast. Curr. Biol. 27:101491–97.e4
    [Google Scholar]
  75. Kõivomägi M, Swaffer MP, Turner JJ, Marinov G, Skotheim JM. 2021. G1 cyclin-Cdk promotes cell cycle entry through localized phosphorylation of RNA polymerase II. Science 374:6565347–51
    [Google Scholar]
  76. Landry BD, Doyle JP, Toczyski DP, Benanti JA. 2012. F-box protein specificity for g1 cyclins is dictated by subcellular localization. PLOS Genet. 8:7e1002851
    [Google Scholar]
  77. Lanz MC, Zatulovskiy E, Swaffer MP, Zhang L, Ilerten I et al. 2021. Increasing cell size remodels the proteome and promotes senescence. bioRxiv 454227. https://doi.org/10.1101/2021.07.29.454227
    [Crossref]
  78. Lengefeld J, Cheng C-W, Maretich P, Blair M, Hagen H et al. 2021. Cell size is a determinant of stem cell potential during aging. Sci. Adv. 7:46eabk0271
    [Google Scholar]
  79. Li Q, Rycaj K, Chen X, Tang DG 2015. Cancer stem cells and cell size: a causal link?. Semin. Cancer Biol. 35:191–99
    [Google Scholar]
  80. Li Y, Liu D, López-Paz C, Olson BJ, Umen JG. 2016. A new class of cyclin dependent kinase in Chlamydomonas is required for coupling cell size to cell division. eLife 5:e10767
    [Google Scholar]
  81. Lin J, Amir A. 2018. Homeostasis of protein and mRNA concentrations in growing cells. Nat. Commun. 9:4496
    [Google Scholar]
  82. Litsios A, Huberts DHEW, Terpstra HM, Guerra P, Schmidt A et al. 2019. Differential scaling between G1 protein production and cell size dynamics promotes commitment to the cell division cycle in budding yeast. Nat. Cell Biol. 21:111382–92
    [Google Scholar]
  83. Liu GY, Sabatini DM. 2020. mTOR at the nexus of nutrition, growth, ageing and disease. Nat. Rev. Mol. Cell Biol. 21:4183–203
    [Google Scholar]
  84. Liu S, Ginzberg MB, Patel N, Hild M, Leung B et al. 2018. Size uniformity of animal cells is actively maintained by a p38 MAPK-dependent regulation of G1-length. eLife 7:e26947
    [Google Scholar]
  85. Liu S, Tan C, Melo-Gavin C, Mark KG, Ginzberg MB et al. 2021. Large cells activate global protein degradation to maintain cell size homeostasis. bioRxiv 467936. https://doi.org/10.1101/2021.11.09.467936
    [Crossref]
  86. Liu X, Oh S, Peshkin L, Kirschner MW. 2020. Computationally enhanced quantitative phase microscopy reveals autonomous oscillations in mammalian cell growth. PNAS 117:4427388–99
    [Google Scholar]
  87. Liu X, Wang X, Yang X, Liu S, Jiang L et al. 2015. Reliable cell cycle commitment in budding yeast is ensured by signal integration. eLife 4:e03977
    [Google Scholar]
  88. Liu X, Yan J, Kirschner MW 2022. Beyond G1/S regulation: how cell size homeostasis is tightly controlled throughout the cell cycle?. bioRxiv 478996. https://doi.org/10.1101/2022.02.03.478996
    [Crossref]
  89. Lloyd AC. 2013. The regulation of cell size. Cell 154:61194–205
    [Google Scholar]
  90. Marguerat S, Bähler J. 2012. Coordinating genome expression with cell size. Trends Genet. 28:11560–65
    [Google Scholar]
  91. Martin SG, Berthelot-Grosjean M. 2009. Polar gradients of the DYRK-family kinase Pom1 couple cell length with the cell cycle. Nature 459:7248852–56
    [Google Scholar]
  92. McNulty JJ, Lew DJ. 2005. Swe1p responds to cytoskeletal perturbation, not bud size, in S. cerevisiae. Curr. Biol. 15:242190–98
    [Google Scholar]
  93. Medina EM, Turner JJ, Gordân R, Skotheim JM, Buchler NE. 2016. Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi. eLife 5:e09492
    [Google Scholar]
  94. Mena A, Medina DA, García-Martínez J, Begley V, Singh A et al. 2017. Asymmetric cell division requires specific mechanisms for adjusting global transcription. Nucleic Acids. Res. 45:2112401–12
    [Google Scholar]
  95. Mesa KR, Kawaguchi K, Cockburn K, Gonzalez D, Boucher J et al. 2018. Homeostatic epidermal stem cell self-renewal is driven by local differentiation. Cell Stem Cell 23:5677–86.e4
    [Google Scholar]
  96. Miettinen TP, Björklund M. 2016. Cellular allometry of mitochondrial functionality establishes the optimal cell size. Dev. Cell 39:3370–82
    [Google Scholar]
  97. Miller ME, Cross FR, Groeger AL, Jameson KL. 2005. Identification of novel and conserved functional and structural elements of the G1 cyclin Cln3 important for interactions with the CDK Cdc28 in Saccharomyces cerevisiae. Yeast 22:131021–36
    [Google Scholar]
  98. Milo R, Phillips R. 2016. Cell Biology by the Numbers New York: Garland Science
    [Google Scholar]
  99. Mitchison JM. 2003. Growth during the cell cycle. Int. Rev. Cytol. 226:165–258
    [Google Scholar]
  100. Moreno DF, Jenkins K, Morlot S, Charvin G, Csikasz-Nagy A, Aldea M. 2019. Proteostasis collapse, a hallmark of aging, hinders the chaperone-Start network and arrests cells in G1. eLife 8:e48240
    [Google Scholar]
  101. Moreno S, Nurse P, Russell P. 1990. Regulation of mitosis by cyclic accumulation of p80cdc25 mitotic inducer in fission yeast. Nature 344:6266549–52
    [Google Scholar]
  102. Moseley JB, Mayeux A, Paoletti A, Nurse P. 2009. A spatial gradient coordinates cell size and mitotic entry in fission yeast. Nature 459:7248857–60
    [Google Scholar]
  103. Mu L, Kang JH, Olcum S, Payer KR, Calistri NL et al. 2020. Mass measurements during lymphocytic leukemia cell polyploidization decouple cell cycle- and cell size-dependent growth. PNAS 117:2715659–65
    [Google Scholar]
  104. Narasimha AM, Kaulich M, Shapiro GS, Choi YJ, Sicinski P, Dowdy SF. 2014. Cyclin D activates the Rb tumor suppressor by mono-phosphorylation. eLife 3:e02872
    [Google Scholar]
  105. Nash R, Tokiwa G, Anand S, Erickson K, Futcher AB. 1988. The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog. EMBO J. 7:134335–46
    [Google Scholar]
  106. Neumann FR, Nurse P. 2007. Nuclear size control in fission yeast. J. Cell Biol. 179:4593–600
    [Google Scholar]
  107. Neurohr GE, Terry RL, Lengefeld J, Bonney M, Brittingham GP et al. 2019. Excessive cell growth causes cytoplasm dilution and contributes to senescence. Cell 176:51083–97.e18
    [Google Scholar]
  108. Novak B, Tyson JJ, Gyorffy B, Csikasz-Nagy A. 2007. Irreversible cell-cycle transitions are due to systems-level feedback. Nat. Cell Biol. 9:7724–28
    [Google Scholar]
  109. Oh S, Lee C, Yang W, Li A, Mukherjee A et al. 2019. Protein and lipid mass concentration measurement in tissues by stimulated Raman scattering microscopy. bioRxiv 629543. https://doi.org/10.1101/629543
    [Crossref]
  110. Olson BJSC, Oberholzer M, Li Y, Zones JM, Kohli HS et al. 2010. Regulation of the Chlamydomonas cell cycle by a stable, chromatin-associated retinoblastoma tumor suppressor complex. Plant Cell 22:103331–47
    [Google Scholar]
  111. Padovan-Merhar O, Nair GP, Biaesch AG, Mayer A, Scarfone S et al. 2015. Single mammalian cells compensate for differences in cellular volume and DNA copy number through independent global transcriptional mechanisms. Mol. Cell 58:2339–52
    [Google Scholar]
  112. Pan KZ, Saunders TE, Flor-Parra I, Howard M, Chang F. 2014. Cortical regulation of cell size by a sizer cdr2p. eLife 3:e02040
    [Google Scholar]
  113. Patterson JO, Rees P, Nurse P. 2019. Noisy cell-size-correlated expression of cyclin B drives probabilistic cell-size homeostasis in fission yeast. Curr. Biol. 29:81379–86.e4
    [Google Scholar]
  114. Perez-Gonzalez NA, Rochman ND, Yao K, Tao J, Le M-TT et al. 2019. YAP and TAZ regulate cell volume. J. Cell Biol. 218:103472–88
    [Google Scholar]
  115. Plaschka C, Larivière L, Wenzeck L, Seizl M, Hemann M et al. 2015. Architecture of the RNA polymerase II-Mediator core initiation complex. Nature 518:7539376–80
    [Google Scholar]
  116. Proulx-Giraldeau F, Skotheim JM. 2022. Evolution of cell size control is canalized towards adders or sizers by cell cycle structure and selective pressures. bioRxiv 488093. https://doi.org/10.1101/2022.04.12.488093
    [Crossref]
  117. Qu Y, Jiang J, Liu X, Wei P, Yang X, Tang C 2019. Cell cycle inhibitor Whi5 records environmental information to coordinate growth and division in yeast. Cell Rep. 29:4987–94.e5
    [Google Scholar]
  118. Rodríguez-Molina JB, Tseng SC, Simonett SP, Taunton J, Ansari AZ. 2016. Engineered covalent inactivation of TFIIH-kinase reveals an elongation checkpoint and results in widespread mRNA stabilization. Mol. Cell 63:3433–44
    [Google Scholar]
  119. Rubin SM, Sage J, Skotheim JM. 2020. Integrating old and new paradigms of G1/S control. Mol. Cell 80:2183–92
    [Google Scholar]
  120. Ruscetti M, Leibold J, Bott MJ, Fennell M, Kulick A et al. 2018. NK cell-mediated cytotoxicity contributes to tumor control by a cytostatic drug combination. Science 362:64211416–22
    [Google Scholar]
  121. Sage J, Mulligan GJ, Attardi LD, Miller A, Chen S et al. 2000. Targeted disruption of the three Rb-related genes leads to loss of G1 control and immortalization. Genes Dev. 14:233037–50
    [Google Scholar]
  122. Sauls JT, Li D, Jun S. 2016. Adder and a coarse-grained approach to cell size homeostasis in bacteria. Curr. Opin. Cell Biol. 38:38–44
    [Google Scholar]
  123. Schmoller KM, Lanz MC, Kim J, Koivomagi M, Qu Y et al. 2022. Whi5 is diluted and protein synthesis does not dramatically increase in pre-Start G1. Mol. Biol. Cell 335
    [Google Scholar]
  124. Schmoller KM, Turner JJ, Kõivomägi M, Skotheim JM. 2015. Dilution of the cell cycle inhibitor Whi5 controls budding-yeast cell size. Nature 526:7572268–72
    [Google Scholar]
  125. Schoenfelder KP, Fox DT. 2015. The expanding implications of polyploidy. J. Cell Biol. 209:4485–91
    [Google Scholar]
  126. Schulz D, Pirkl N, Lehmann E, Cramer P. 2014. Rpb4 subunit functions mainly in mRNA synthesis by RNA polymerase II. J. Biol. Chem. 289:2517446–52
    [Google Scholar]
  127. Scotchman E, Kume K, Navarro FJ, Nurse P. 2021. Identification of mutants with increased variation in cell size at onset of mitosis in fission yeast. J. Cell Sci. 134:3jcs251769
    [Google Scholar]
  128. Serrano-Mislata A, Schiessl K, Sablowski R. 2015. Active control of cell size generates spatial detail during plant organogenesis. Curr. Biol. 25:222991–96
    [Google Scholar]
  129. Sharpless NE, Sherr CJ. 2015. Forging a signature of in vivo senescence. Nat. Rev. Cancer 15:7397–408
    [Google Scholar]
  130. Skotheim JM, Di Talia S, Siggia ED, Cross FR. 2008. Positive feedback of G1 cyclins ensures coherent cell cycle entry. Nature 454:7202291–96
    [Google Scholar]
  131. Slattery ML, Lundgreen A, Herrick JS, Kadlubar S, Caan BJet al 2012. Genetic variation in bone morphogenetic protein and colon and rectal cancer. Int. J. Cancer 130:365364
    [Google Scholar]
  132. Slobodin B, Bahat A, Sehrawat U, Becker-Herman S, Zuckerman B et al. 2020. Transcription dynamics regulate poly(A) tails and expression of the RNA degradation machinery to balance mRNA levels. Mol. Cell 78:3434–44.e5
    [Google Scholar]
  133. Soifer I, Barkai N. 2014. Systematic identification of cell size regulators in budding yeast. Mol. Syst. Biol. 10:761
    [Google Scholar]
  134. Soifer I, Robert L, Amir A. 2016. Single-cell analysis of growth in budding yeast and bacteria reveals a common size regulation strategy. Curr. Biol. 26:3356–61
    [Google Scholar]
  135. Sommer RA, DeWitt JT, Tan R, Kellogg DR. 2021. Growth-dependent signals drive an increase in early G1 cyclin concentration to link cell cycle entry with cell growth. eLife 10:e64364
    [Google Scholar]
  136. Son S, Tzur A, Weng Y, Jorgensen P, Kim J et al. 2012. Direct observation of mammalian cell growth and size regulation. Nat. Methods 9:9910–12
    [Google Scholar]
  137. Sun M, Schwalb B, Schulz D, Pirkl N, Etzold S et al. 2012. Comparative dynamic transcriptome analysis (cDTA) reveals mutual feedback between mRNA synthesis and degradation. Genome Res. 22:71350–59
    [Google Scholar]
  138. Sun X-M, Bowman A, Priestman M, Bertaux F, Martinez-Segura A et al. 2020. Size-dependent increase in RNA polymerase II initiation rates mediates gene expression scaling with cell size. Curr. Biol. 30:71217–30.e7
    [Google Scholar]
  139. Swaffer MP, Kim J, Chandler-Brown D, Langhinrichs M, Marinov GK et al. 2021a. Transcriptional and chromatin-based partitioning mechanisms uncouple protein scaling from cell size. Mol. Cell 81:234861–75.e7
    [Google Scholar]
  140. Swaffer MP, Marinov GK, Zheng H, Jones AW, Greenwood J et al. 2021b. RNA polymerase II dynamics and mRNA stability feedback determine mRNA scaling with cell size. bioRxiv 461005. https://doi.org/10.1101/2021.09.20.461005
    [Crossref]
  141. Taheri-Araghi S, Bradde S, Sauls JT, Hill NS, Levin PA et al. 2015. Cell-size control and homeostasis in bacteria. Curr. Biol. 25:3385–91
    [Google Scholar]
  142. Tan C, Ginzberg MB, Webster R, Iyengar S, Liu S et al. 2021. Cell size homeostasis is maintained by CDK4-dependent activation of p38 MAPK. Dev. Cell 56:121756–69.e7
    [Google Scholar]
  143. Terhorst A, Sandikci A, Neurohr GE, Whittaker CA, Szórádi T et al. 2021. The environmental stress response regulates ribosome content in cell cycle-arrested S. cerevisiae. bioRxiv 444167. https://doi.org/10.1101/2021.05.14.444167
    [Crossref]
  144. Thornton TM, Rincon M. 2009. Non-classical p38 map kinase functions: cell cycle checkpoints and survival. Int. J. Biol. Sci. 5:144–51
    [Google Scholar]
  145. Tomás-Loba A, Manieri E, González-Terán B, Mora A, Leiva-Vega L et al. 2019. p38γ is essential for cell cycle progression and liver tumorigenesis. Nature 568:7753557–60
    [Google Scholar]
  146. Topacio BR, Zatulovskiy E, Cristea S, Xie S, Tambo CS et al. 2019. Cyclin D-Cdk4,6 drives cell-cycle progression via the retinoblastoma protein's C-terminal helix. Mol. Cell 74:4758–70.e4
    [Google Scholar]
  147. Turner JJ, Ewald JC, Skotheim JM. 2012. Cell size control in yeast. Curr. Biol. 22:9R350–59
    [Google Scholar]
  148. Tyers M, Tokiwa G, Futcher B. 1993. Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins. EMBO J. 12:51955–68
    [Google Scholar]
  149. Tyers M, Tokiwa G, Nash R, Futcher B. 1992. The Cln3-Cdc28 kinase complex of S. cerevisiae is regulated by proteolysis and phosphorylation. EMBO J. 11:51773–84
    [Google Scholar]
  150. Tyson JJ, Diekmann O. 1986. Sloppy size control of the cell division cycle. J. Theor. Biol. 118:4405–26
    [Google Scholar]
  151. Tzur A, Kafri R, LeBleu VS, Lahav G, Kirschner MW. 2009. Cell growth and size homeostasis in proliferating animal cells. Science 325:5937167–71
    [Google Scholar]
  152. Umen JG, Goodenough UW. 2001. Control of cell division by a retinoblastoma protein homolog in Chlamydomonas. Genes Dev. 15:131652–61
    [Google Scholar]
  153. Uroz M, Wistorf S, Serra-Picamal X, Conte V, Sales-Pardo M et al. 2018. Regulation of cell cycle progression by cell-cell and cell-matrix forces. Nat. Cell Biol. 20:6646–54
    [Google Scholar]
  154. Varsano G, Wang Y, Wu M. 2017. Probing mammalian cell size homeostasis by channel-assisted cell reshaping. Cell Rep. 20:2397–410
    [Google Scholar]
  155. Vergés E, Colomina N, Garí E, Gallego C, Aldea M. 2007. Cyclin Cln3 is retained at the ER and released by the J chaperone Ydj1 in late G1 to trigger cell cycle entry. Mol. Cell 26:5649–62
    [Google Scholar]
  156. Verkest A, Weinl C, Inzé D, De Veylder L, Schnittger A. 2005. Switching the cell cycle. Kip-related proteins in plant cell cycle control. Plant Physiol. 139:31099–106
    [Google Scholar]
  157. Wang H, Carey LB, Cai Y, Wijnen H, Futcher B. 2009. Recruitment of Cln3 cyclin to promoters controls cell cycle entry via histone deacetylase and other targets. PLOS Biol. 7:9e1000189
    [Google Scholar]
  158. Warfield L, Ramachandran S, Baptista T, Devys D, Tora L, Hahn S. 2017. Transcription of nearly all yeast RNA polymerase II-transcribed genes is dependent on transcription factor TFIID. Mol. Cell 68:1118–29.e5
    [Google Scholar]
  159. Willis L, Refahi Y, Wightman R, Landrein B, Teles J et al. 2016. Cell size and growth regulation in the Arabidopsis thaliana apical stem cell niche. PNAS 113:51E8238–46
    [Google Scholar]
  160. Wilson GA, Sava G, Vuina K, Huard C, Meneguello L et al. 2021. Active growth signalling promotes cancer cell sensitivity to the CDK7 inhibitor ICEC0942. bioRxiv 459733. https://doi.org/10.1101/2021.09.10.459733
    [Crossref]
  161. Wood E, Nurse P. 2013. Pom1 and cell size homeostasis in fission yeast. Cell Cycle 12:193228–36
    [Google Scholar]
  162. Xie S, Skotheim JM. 2020. A G1 sizer coordinates growth and division in the mouse epidermis. Curr. Biol. 30:5916–24.e2
    [Google Scholar]
  163. Xie S, Skotheim JM. 2021. Cell-size control: chromatin-based titration primes inhibitor dilution. Curr. Biol. 31:19R1127–29
    [Google Scholar]
  164. Yahya G, Menges P, Anggraini Ngandiri D, Schulz D, Wallek A et al. 2021. Scaling of cellular proteome with ploidy. bioRxiv 2021.05.06.442919. https://doi.org/10.1101/2021.05.06.442919
    [Crossref]
  165. Yahya G, Parisi E, Flores A, Gallego C, Aldea M. 2014. A Whi7-anchored loop controls the G1 Cdk-cyclin complex at start. Mol. Cell 53:1115–26
    [Google Scholar]
  166. Yang J, Dungrawala H, Hua H, Manukyan A, Abraham L et al. 2011. Cell size and growth rate are major determinants of replicative lifespan. Cell Cycle 10:1144–55
    [Google Scholar]
  167. Yang J, Wang Z, Liu X, Li H, Ouyang Q. 2018. Yeast replicative aging leads to permanent cell cycle arrest in G1 effectuated by the start repressor Whi5. bioRxiv 353664. https://doi.org/10.1101/353664
    [Crossref]
  168. Yao G, Lee TJ, Mori S, Nevins JR, You L. 2008. A bistable Rb-E2F switch underlies the restriction point. Nat. Cell Biol. 10:4476–82
    [Google Scholar]
  169. Zatulovskiy E, Skotheim JM. 2020. On the molecular mechanisms regulating animal cell size homeostasis. Trends Genet. 36:5360–72
    [Google Scholar]
  170. Zatulovskiy E, Zhang S, Berenson DF, Topacio BR, Skotheim JM. 2020. Cell growth dilutes the cell cycle inhibitor Rb to trigger cell division. Science 369:6502466–71
    [Google Scholar]
  171. Zhou Y, Li J, Xu K, Hu SX, Benedict WF, Xu HJ. 1994. Further characterization of retinoblastoma gene-mediated cell growth and tumor suppression in human cancer cells. PNAS 91:104165–69
    [Google Scholar]
  172. Zhurinsky J, Leonhard K, Watt S, Marguerat S, Bähler J, Nurse P. 2010. A coordinated global control over cellular transcription. Curr. Biol. 20:222010–15
    [Google Scholar]
/content/journals/10.1146/annurev-cellbio-120219-040142
Loading
/content/journals/10.1146/annurev-cellbio-120219-040142
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error