G1/S-specific cyclin Cln3 is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that is encoded by the ''CLN3''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

. The Cln3 protein is a

budding yeast ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been ...

G1 cyclin that controls the timing of ''Start'', the point of commitment to a mitotic cell cycle. It is an upstream regulator of the other G1 cyclins, and it is thought to be the key regulator linking cell growth to cell cycle progression. It is a 65 kD, unstable protein; like other

cyclin Cyclin is a family of proteins that controls the progression of a cell through the cell cycle by activating cyclin-dependent kinase (CDK) enzymes or group of enzymes required for synthesis of cell cycle. Etymology Cyclins were originally disco ...

s, it functions by binding and activating

cyclin-dependent kinase Cyclin-dependent kinases (CDKs) are the families of protein kinases first discovered for their role in regulating the cell cycle. They are also involved in regulating transcription, mRNA processing, and the differentiation of nerve cells. They ...

(CDK).

Cln3 in ''Start'' regulation

Cln3 regulates ''Start'', the point at which

commit to the

G1/S transition The G1/S transition is a stage in the cell cycle at the boundary between the G1 phase, in which the cell grows, and the S phase, during which DNA is replicated. It is governed by cell cycle checkpoints to ensure cell cycle integrity and the subs ...

and thus a round of mitotic division. It was first identified as a gene controlling this process in the 1980s; research over the past few decades has provided a mechanistic understanding of its function.

Identification of ''CLN3'' gene

The ''CLN3'' gene was originally identified as the ''whi1-1'' allele in a screen for small size mutants of

Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...

(for Cln3's role in size control, see

below Below may refer to: *Earth * Ground (disambiguation) *Soil *Floor * Bottom (disambiguation) *Less than *Temperatures below freezing *Hell or underworld People with the surname *Ernst von Below (1863–1955), German World War I general *Fred Below ...

). This screen was inspired by a similar study in

Schizosaccharomyces pombe ''Schizosaccharomyces pombe'', also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped. Cells typically measur ...

, in which the '' Wee1'' gene was identified as an inhibitor of cell cycle progression that maintained normal cell size. Thus, the ''WHI1'' gene was at first thought to perform a size control function analogous to that of ''Wee1'' in ''pombe''. However, it was later found that ''WHI1'' was in fact a positive regulator of ''Start'', as its deletion caused cells to delay in G1 and grow larger than wild-type cells. The original ''WHI1-1'' allele (changed from ''whi1-1'' because it is a dominant allele) in fact contained a nonsense mutation that removed a degradation-promoting

PEST sequence A PEST sequence is a peptide sequence that is rich in proline (P), glutamic acid (E), serine (S), and threonine (T). This sequence is associated with proteins that have a short intracellular half-life; therefore, it is hypothesized that the PEST s ...

from the Whi1 protein and thus accelerated G1 progression. ''WHI1'' was furthermore found to be a cyclin homologue, and it was shown that simultaneous deletion of ''WHI1''—renamed ''CLN3''—and the previously identified G1 cyclins, ''CLN1'' and ''CLN2'', caused permanent G1 arrest. This showed that the three G1 cyclins were responsible for controlling ''Start'' entry in budding yeast.

G1-S transition

The three G1 cyclins collaborate to drive yeast cells through the G1-S transition, i.e. to enter

S-phase S phase (Synthesis Phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during ...

and begin

DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritan ...

. The current model of the gene regulatory network controlling the G1-S transition is shown in Figure 1. The key targets of the G1 cyclins in this transition are the

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...

s SBF and MBF (not shown in the diagram), as well as the B-type cyclin inhibitor

Sic1 Sic1, a protein, is a stoichiometric inhibitor of Cdk1-Clb ( B-type cyclins) complexes in the budding yeast ''Saccharomyces cerevisiae''. Because B-type cyclin-Cdk1 complexes are the drivers of S-phase initiation, Sic1 prevents premature S-phase ...

. Cln-CDKs activate SBF by phosphorylating and promoting nuclear export of its inhibitor, Whi5, which associates with promoter-bound SBF. The precise mechanism of MBF activation is unknown. Together, these transcription factors promote the expression of over 200 genes, which encode the proteins necessary for carrying out the biochemical activities of S-phase. These include the S-phase cyclins Clb5 and Clb6, which bind CDK to phosphorylate S-phase targets. However, Clb5,6-CDK complexes are inhibited by Sic1, so S-phase initiation requires phosphorylation and degradation of Sic1 by Cln1,2-CDK to proceed fully.

Cln3 activates a Cln1,2 positive feedback loop

Although all three G1 cyclins are necessary for normal regulation of ''Start'' and the G1-S transition, Cln3 activity seems to be the deciding factor in S-phase initiation, with Cln1 and Cln2 serving to actuate the Cln3-based decision to transit ''Start''. It was found early on that Cln3 activity induced expression of Cln1 and Cln2. Furthermore, Cln3 was a stronger activator ''Start'' transit than Cln1 and Cln2, even though Cln3-CDK had an inherently weaker

kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

activity than the other Clns. This indicated that Cln3 was an upstream regulator of Cln1 and Cln2. Furthermore, it was found, as shown in Figure 1, that Cln1 and Cln2 could activate their own transcription via SBF, completing a

positive feedback Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop which exacerbates the effects of a small disturbance. That is, the effects of a perturbation on a system include an increase in th ...

loop that could contribute to rapid activation and S-phase entry. Thus, ''Start'' transit seems to rely on reaching a sufficient level of Cln3-CDK activity to induce the Cln1,2 positive feedback loop, which rapidly increases SBF/MBF and Cln1,2 activity, allowing a switch-like G1-S transition. The role of positive feedback in this process has been challenged, but recent experiments have confirmed its importance for rapid inactivation and nuclear export of Whi5, which is the molecular basis of commitment to S-phase.

Cln3 and cell size control

As discussed above, Cln3 was originally identified as a regulator of budding yeast cell size. The elucidation of the mechanisms by which it regulates ''Start'' has revealed a means for it to link cell size to cell cycle progression, but questions remain as to how it actually senses cell size.

''Start'' requires a threshold cell size

The simple observation that cells of a given type are similar in size, and the question of how this similarity is maintained, has long fascinated

cell biologists Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and ...

. The study of cell size control in budding yeast began in earnest in the mid 1970s, when the regulation of the budding yeast cell cycle was first being elucidated by

Lee Hartwell Leland Harrison (Lee) Hartwell (born October 30, 1939 in Los Angeles, California) is former president and director of the Fred Hutchinson Cancer Research Center in Seattle, Washington. He shared the 2001 Nobel Prize in Physiology or Medicine wit ...

and colleagues. Seminal work in 1977 found that yeast cells maintain a constant size by delaying their entry into the cell cycle (as assayed by budding) until they have grown to a threshold size. Later worked refined this result to show that ''Start'' specifically, rather than some other aspect of the G1-S transition, is controlled by the size threshold.

Translational size sensing

That ''Start'' transit requires the attainment of a threshold cell size directly implies that yeast cells measure their own size, so that they can use that information to regulate ''Start''. A favored model for how yeast cells, as well as cells of other species, measure their size relies on the detection of overall

translation Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...

rate. Essentially, since cell growth consists, to a great extent, of the synthesis of ribosomes to produce more proteins, the overall rate of protein production should reflect cell size. Thus, a single protein that is produced at a constant rate relative to total protein production capacity will be produced in higher quantities as the cell grows. If this protein promotes cell cycle progression (''Start'' in the case of yeast), then it will link cell cycle progression to translation rate and, therefore, cell size. Importantly, this protein must be unstable, so that its levels depend on its ''current'' translation rate, rather than the rate of translation over time. Furthermore, since the cell grows in volume as well as mass, the concentration of this size sensor will remain constant with growth, so its activity must be compared against something that does not change with cell growth. Genomic DNA was suggested as such a standard early on, because it is (by definition) present in a constant quantity until the start of DNA replication. How this occurs remains a major question in current studies of size control (see

). Before the identification of Cln3 and its function, accrued evidence indicated that such translational size sensing operated in yeast. First, it was confirmed that the total rate of protein synthesis per cell increases with growth, a fundamental prerequisite for this model. It was later shown that treatment with the protein synthesis inhibitor

cycloheximide Cycloheximide is a naturally occurring fungicide produced by the bacterium '' Streptomyces griseus''. Cycloheximide exerts its effects by interfering with the translocation step in protein synthesis (movement of two tRNA molecules and mRNA in rel ...

delayed ''Start'' in yeast, indicating that translation rate controlled ''Start''. Finally, it was also shown that this delay occurred even with short pulses of cycloheximide, confirming that an unstable activating protein was required for ''Start''.

Cln3 as size sensor

The model of budding yeast size control, in which a threshold size for ''Start'' entry is detected by a translational size sensor, required a "sizer" protein; the properties of Cln3 made it the prime candidate for that role from the time of its discovery. First, it was a critical ''Start'' activator, as G1 length varied inversely with Cln3 expression and activity levels. Second, it was expressed nearly constitutively throughout the cell cycle and in G1 in particular—unusual for cyclins, which (as their name suggests) oscillate in expression with the cell cycle. These two properties meant that Cln3 could serve as a ''Start'' activator that depended on total translation rate. Finally, Cln3 was also shown to be highly unstable, the third necessary property of a translational sizer (as discussed above). Thus, Cln3 seems to be the size sensor in budding yeast, as it exhibits the necessary properties of a translational sizer and is the most upstream regulator of ''Start''. A critical question remains, however, as to how its activity is rendered size dependent. As noted above, any translational size sensor should be at constant concentration, and thus constant activity, in the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...

as cells grow. In order to detect its size, the cell must compare the absolute number of sizer molecules to some non-growing standard, with the genome the obvious choice for such a standard. It was originally thought that yeast accomplished this with Cln3 by localizing it (and its target, Whi5) to the nucleus: nuclear volume was assumed to scale with genome content, so that an increasing concentration of Cln3 in the nucleus could indicate increasing Cln3 molecules relative to the genome. However, the nucleus has recently been shown to grow during G1, irrespective of genome content, undermining this model. Recent experiments have suggested that Cln3 activity could be titrated directly against genomic DNA, through its DNA-bound interaction with SBF- Whi5 complexes. Finally, other models exist that do not rely on comparison of Cln3 levels to DNA. One posits a non-linear relationship between total translation rate and Cln3 translation rate caused by an Upstream open reading frame; another suggests that the increase in Cln3 activity at the end of G1 relies on competition for the chaperone protein Ydj1, which otherwise holds Cln3 molecules in the

Endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ...

References

{{reflist , colwidth=35em , refs= {{cite journal , vauthors = Tyers M, Tokiwa G, Futcher B , title = Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins , journal = The EMBO Journal , volume = 12 , issue = 5 , pages = 1955–68 , date = May 1993 , pmid = 8387915 , pmc = 413417 , doi = 10.1002/j.1460-2075.1993.tb05845.x {{cite journal , vauthors = Futcher B , title = Cyclins and the wiring of the yeast cell cycle , journal = Yeast , volume = 12 , issue = 16 , pages = 1635–46 , date = December 1996 , pmid = 9123966 , doi = 10.1002/(SICI)1097-0061(199612)12:16<1635::AID-YEA83>3.0.CO;2-O , s2cid = 39864643 {{cite journal , vauthors = Jorgensen P, Tyers M , title = How cells coordinate growth and division , journal = Current Biology , volume = 14 , issue = 23 , pages = R1014–27 , date = December 2004 , pmid = 15589139 , doi = 10.1016/j.cub.2004.11.027 , doi-access = free {{cite journal , vauthors = Tyers M, Tokiwa G, Nash R, Futcher B , title = The Cln3-Cdc28 kinase complex of S. cerevisiae is regulated by proteolysis and phosphorylation , journal = The EMBO Journal , volume = 11 , issue = 5 , pages = 1773–84 , date = May 1992 , pmid = 1316273 , pmc = 556635 , doi = 10.1002/j.1460-2075.1992.tb05229.x {{cite journal , vauthors = Cross FR, Blake CM , title = The yeast Cln3 protein is an unstable activator of Cdc28 , journal = Molecular and Cellular Biology , volume = 13 , issue = 6 , pages = 3266–71 , date = June 1993 , pmid = 8497251 , pmc = 359776 , doi = 10.1128/MCB.13.6.3266 {{cite journal , vauthors = Carter BL, Sudbery PE , title = Small-sized mutants of Saccharomyces cerevisiae , journal = Genetics , volume = 96 , issue = 3 , pages = 561–6 , date = November 1980 , doi = 10.1093/genetics/96.3.561 , pmid = 7021310 , pmc = 1214361 {{cite journal , vauthors = Sudbery PE, Goodey AR, Carter BL , title = Genes which control cell proliferation in the yeast Saccharomyces cerevisiae , journal = Nature , volume = 288 , issue = 5789 , pages = 401–4 , date = November 1980 , pmid = 7001255 , doi = 10.1038/288401a0 , bibcode = 1980Natur.288..401S , s2cid = 4270472 {{cite journal , vauthors = Hartwell LH, Unger MW , title = Unequal division in Saccharomyces cerevisiae and its implications for the control of cell division , journal = The Journal of Cell Biology , volume = 75 , issue = 2 Pt 1 , pages = 422–35 , date = November 1977 , pmid = 400873 , pmc = 2109951 , doi = 10.1083/jcb.75.2.422 {{cite journal , vauthors = Johnston GC, Pringle JR, Hartwell LH , title = Coordination of growth with cell division in the yeast Saccharomyces cerevisiae , journal = Experimental Cell Research , volume = 105 , issue = 1 , pages = 79–98 , date = March 1977 , pmid = 320023 , doi = 10.1016/0014-4827(77)90154-9 {{cite journal , vauthors = Di Talia S, Skotheim JM, Bean JM, Siggia ED, Cross FR , title = The effects of molecular noise and size control on variability in the budding yeast cell cycle , journal = Nature , volume = 448 , issue = 7156 , pages = 947–51 , date = August 2007 , pmid = 17713537 , doi = 10.1038/nature06072 , bibcode = 2007Natur.448..947T , s2cid = 62782023 {{cite journal , vauthors = Nurse P , title = Genetic control of cell size at cell division in yeast , journal = Nature , volume = 256 , issue = 5518 , pages = 547–51 , date = August 1975 , pmid = 1165770 , doi = 10.1038/256547a0 , bibcode = 1975Natur.256..547N , s2cid = 4157822 {{cite journal , vauthors = Nash R, Tokiwa G, Anand S, Erickson K, Futcher AB , title = The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog , journal = The EMBO Journal , volume = 7 , issue = 13 , pages = 4335–46 , date = December 1988 , pmid = 2907481 , pmc = 455150 , doi = 10.1002/j.1460-2075.1988.tb03332.x {{cite journal , vauthors = Cross FR , title = DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae , journal = Molecular and Cellular Biology , volume = 8 , issue = 11 , pages = 4675–84 , date = November 1988 , pmid = 3062366 , pmc = 365557 , doi = 10.1128/MCB.8.11.4675 {{cite journal , vauthors = Richardson HE, Wittenberg C, Cross F, Reed SI , title = An essential G1 function for cyclin-like proteins in yeast , journal = Cell , volume = 59 , issue = 6 , pages = 1127–33 , date = December 1989 , pmid = 2574633 , doi = 10.1016/0092-8674(89)90768-X , doi-access = free {{cite journal , vauthors = Hadwiger JA, Wittenberg C, Richardson HE, de Barros Lopes M, Reed SI , title = A family of cyclin homologs that control the G1 phase in yeast , journal = Proceedings of the National Academy of Sciences of the United States of America , volume = 86 , issue = 16 , pages = 6255–9 , date = August 1989 , pmid = 2569741 , pmc = 297816 , doi = 10.1073/pnas.86.16.6255 , bibcode = 1989PNAS...86.6255H , doi-access = free {{cite journal , vauthors = Dirick L, Nasmyth K , title = Positive feedback in the activation of G1 cyclins in yeast , journal = Nature , volume = 351 , issue = 6329 , pages = 754–7 , date = June 1991 , pmid = 1829507 , doi = 10.1038/351754a0 , bibcode = 1991Natur.351..754D , s2cid = 4363524 {{cite journal , vauthors = Cross FR, Tinkelenberg AH , title = A potential positive feedback loop controlling CLN1 and CLN2 gene expression at the start of the yeast cell cycle , journal = Cell , volume = 65 , issue = 5 , pages = 875–83 , date = May 1991 , pmid = 2040016 , doi = 10.1016/0092-8674(91)90394-E , s2cid = 27933669 {{cite journal , vauthors = Stuart D, Wittenberg C , title = CLN3, not positive feedback, determines the timing of CLN2 transcription in cycling cells , journal = Genes & Development , volume = 9 , issue = 22 , pages = 2780–94 , date = November 1995 , pmid = 7590253 , doi = 10.1101/gad.9.22.2780 , doi-access = free {{cite journal , vauthors = Dirick L, Böhm T, Nasmyth K , title = Roles and regulation of Cln-Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae , journal = The EMBO Journal , volume = 14 , issue = 19 , pages = 4803–13 , date = October 1995 , pmid = 7588610 , pmc = 394578 , doi = 10.1002/j.1460-2075.1995.tb00162.x {{cite journal , vauthors = Skotheim JM, Di Talia S, Siggia ED, Cross FR , title = Positive feedback of G1 cyclins ensures coherent cell cycle entry , journal = Nature , volume = 454 , issue = 7202 , pages = 291–6 , date = July 2008 , pmid = 18633409 , pmc = 2606905 , doi = 10.1038/nature07118 , bibcode = 2008Natur.454..291S {{cite journal , vauthors = Doncic A, Falleur-Fettig M, Skotheim JM , title = Distinct interactions select and maintain a specific cell fate , journal = Molecular Cell , volume = 43 , issue = 4 , pages = 528–39 , date = August 2011 , pmid = 21855793 , pmc = 3160603 , doi = 10.1016/j.molcel.2011.06.025 {{cite journal , vauthors = Nasmyth K, Dirick L , title = The role of SWI4 and SWI6 in the activity of G1 cyclins in yeast , journal = Cell , volume = 66 , issue = 5 , pages = 995–1013 , date = September 1991 , pmid = 1832338 , doi = 10.1016/0092-8674(91)90444-4 , s2cid = 28069530 {{cite journal , vauthors = Dirick L, Moll T, Auer H, Nasmyth K , title = A central role for SWI6 in modulating cell cycle Start-specific transcription in yeast , journal = Nature , volume = 357 , issue = 6378 , pages = 508–13 , date = June 1992 , pmid = 1608451 , doi = 10.1038/357508a0 , bibcode = 1992Natur.357..508D , s2cid = 496238 {{cite journal , vauthors = Koch C, Moll T, Neuberg M, Ahorn H, Nasmyth K , title = A role for the transcription factors Mbp1 and Swi4 in progression from G1 to S phase , journal = Science , volume = 261 , issue = 5128 , pages = 1551–7 , date = September 1993 , pmid = 8372350 , doi = 10.1126/science.8372350 , bibcode = 1993Sci...261.1551K {{cite journal , vauthors = Wijnen H, Landman A, Futcher B , title = The G(1) cyclin Cln3 promotes cell cycle entry via the transcription factor Swi6 , journal = Molecular and Cellular Biology , volume = 22 , issue = 12 , pages = 4402–18 , date = June 2002 , pmid = 12024050 , pmc = 133883 , doi = 10.1128/mcb.22.12.4402-4418.2002 {{cite journal , vauthors = Bean JM, Siggia ED, Cross FR , title = High functional overlap between MluI cell-cycle box binding factor and Swi4/6 cell-cycle box binding factor in the G1/S transcriptional program in Saccharomyces cerevisiae , journal = Genetics , volume = 171 , issue = 1 , pages = 49–61 , date = September 2005 , pmid = 15965243 , pmc = 1456534 , doi = 10.1534/genetics.105.044560 {{cite journal , vauthors = Ferrezuelo F, Colomina N, Futcher B, Aldea M , title = The transcriptional network activated by Cln3 cyclin at the G1-to-S transition of the yeast cell cycle , journal = Genome Biology , volume = 11 , issue = 6 , pages = R67 , year = 2010 , pmid = 20573214 , pmc = 2911115 , doi = 10.1186/gb-2010-11-6-r67 {{cite journal , vauthors = Jorgensen P, Nishikawa JL, Breitkreutz BJ, Tyers M , title = Systematic identification of pathways that couple cell growth and division in yeast , journal = Science , volume = 297 , issue = 5580 , pages = 395–400 , date = July 2002 , pmid = 12089449 , doi = 10.1126/science.1070850 , bibcode = 2002Sci...297..395J , s2cid = 32010679 {{cite journal , vauthors = de Bruin RA, McDonald WH, Kalashnikova TI, Yates J, Wittenberg C , title = Cln3 activates G1-specific transcription via phosphorylation of the SBF bound repressor Whi5 , journal = Cell , volume = 117 , issue = 7 , pages = 887–98 , date = June 2004 , pmid = 15210110 , doi = 10.1016/j.cell.2004.05.025 , doi-access = free {{cite journal , vauthors = Costanzo M, Nishikawa JL, Tang X, Millman JS, Schub O, Breitkreuz K, Dewar D, Rupes I, Andrews B, Tyers M , title = CDK activity antagonizes Whi5, an inhibitor of G1/S transcription in yeast , journal = Cell , volume = 117 , issue = 7 , pages = 899–913 , date = June 2004 , pmid = 15210111 , doi = 10.1016/j.cell.2004.05.024 , doi-access = free {{cite journal , vauthors = Koch C, Schleiffer A, Ammerer G, Nasmyth K , title = Switching transcription on and off during the yeast cell cycle: Cln/Cdc28 kinases activate bound transcription factor SBF (Swi4/Swi6) at start, whereas Clb/Cdc28 kinases displace it from the promoter in G2 , journal = Genes & Development , volume = 10 , issue = 2 , pages = 129–41 , date = January 1996 , pmid = 8566747 , doi = 10.1101/gad.10.2.129 , doi-access = free {{cite journal , vauthors = Cosma MP, Tanaka T, Nasmyth K , title = Ordered recruitment of transcription and chromatin remodeling factors to a cell cycle- and developmentally regulated promoter , journal = Cell , volume = 97 , issue = 3 , pages = 299–311 , date = April 1999 , pmid = 10319811 , doi = 10.1016/S0092-8674(00)80740-0 , doi-access = free {{cite journal , vauthors = Schwob E, Böhm T, Mendenhall MD, Nasmyth K , title = The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae , journal = Cell , volume = 79 , issue = 2 , pages = 233–44 , date = October 1994 , pmid = 7954792 , doi = 10.1016/0092-8674(94)90193-7 , s2cid = 34939988 {{cite journal , vauthors = Schneiderman MH, Dewey WC, Highfield DP , title = Inhibition of DNA synthesis in synchronized Chinese hamster cells treated in G1 with cycloheximide , journal = Experimental Cell Research , volume = 67 , issue = 1 , pages = 147–55 , date = July 1971 , pmid = 5106077 , doi = 10.1016/0014-4827(71)90630-6 {{cite journal , vauthors = Donachie WD , title = Relationship between cell size and time of initiation of DNA replication , journal = Nature , volume = 219 , issue = 5158 , pages = 1077–9 , date = September 1968 , pmid = 4876941 , doi = 10.1038/2191077a0 , bibcode = 1968Natur.219.1077D , s2cid = 4215584 {{cite journal , vauthors = Elliott SG, McLaughlin CS , title = Rate of macromolecular synthesis through the cell cycle of the yeast Saccharomyces cerevisiae , journal = Proceedings of the National Academy of Sciences of the United States of America , volume = 75 , issue = 9 , pages = 4384–8 , date = September 1978 , pmid = 360219 , pmc = 336119 , doi = 10.1073/pnas.75.9.4384 , bibcode = 1978PNAS...75.4384E , doi-access = free {{cite journal , vauthors = Popolo L, Vanoni M, Alberghina L , title = Control of the yeast cell cycle by protein synthesis , journal = Experimental Cell Research , volume = 142 , issue = 1 , pages = 69–78 , date = November 1982 , pmid = 6754401 , doi = 10.1016/0014-4827(82)90410-4 {{cite journal , vauthors = Moore SA , title = Kinetic evidence for a critical rate of protein synthesis in the Saccharomyces cerevisiae yeast cell cycle , journal = The Journal of Biological Chemistry , volume = 263 , issue = 20 , pages = 9674–81 , date = July 1988 , doi = 10.1016/S0021-9258(19)81570-3 , pmid = 3290211 , doi-access = free {{cite journal , vauthors = Shilo B, Riddle VG, Pardee AB , title = Protein turnover and cell-cycle initiation in yeast , journal = Experimental Cell Research , volume = 123 , issue = 2 , pages = 221–7 , date = October 1979 , pmid = 387426 , doi = 10.1016/0014-4827(79)90462-2 {{cite journal , vauthors = Miller ME, Cross FR , title = Distinct subcellular localization patterns contribute to functional specificity of the Cln2 and Cln3 cyclins of Saccharomyces cerevisiae , journal = Molecular and Cellular Biology , volume = 20 , issue = 2 , pages = 542–55 , date = January 2000 , pmid = 10611233 , pmc = 85127 , doi = 10.1128/mcb.20.2.542-555.2000 {{cite journal , vauthors = Edgington NP, Futcher B , title = Relationship between the function and the location of G1 cyclins in S. cerevisiae , journal = Journal of Cell Science , volume = 114 , issue = Pt 24 , pages = 4599–611 , date = December 2001 , doi = 10.1242/jcs.114.24.4599 , pmid = 11792824 {{cite journal , vauthors = Jorgensen P, Edgington NP, Schneider BL, Rupes I, Tyers M, Futcher B , title = The size of the nucleus increases as yeast cells grow , journal = Molecular Biology of the Cell , volume = 18 , issue = 9 , pages = 3523–32 , date = September 2007 , pmid = 17596521 , pmc = 1951755 , doi = 10.1091/mbc.E06-10-0973 {{cite journal , vauthors = Vergés E, Colomina N, Garí E, Gallego C, Aldea M , title = Cyclin Cln3 is retained at the ER and released by the J chaperone Ydj1 in late G1 to trigger cell cycle entry , journal = Molecular Cell , volume = 26 , issue = 5 , pages = 649–62 , date = June 2007 , pmid = 17560371 , doi = 10.1016/j.molcel.2007.04.023 , doi-access = free {{cite journal , vauthors = Polymenis M, Schmidt EV , title = Coupling of cell division to cell growth by translational control of the G1 cyclin CLN3 in yeast , journal = Genes & Development , volume = 11 , issue = 19 , pages = 2522–31 , date = October 1997 , pmid = 9334317 , pmc = 316559 , doi = 10.1101/gad.11.19.2522 {{cite journal , vauthors = Wang H, Carey LB, Cai Y, Wijnen H, Futcher B , title = Recruitment of Cln3 cyclin to promoters controls cell cycle entry via histone deacetylase and other targets , journal = PLOS Biology , volume = 7 , issue = 9 , pages = e1000189 , date = September 2009 , pmid = 19823669 , pmc = 2730028 , doi = 10.1371/journal.pbio.1000189 Fungal proteins Saccharomyces cerevisiae genes