Abstract
Exogenous signals induce cells to enter the specialized cell division process of meiosis, which produces haploid gametes from diploid progenitor cells. Once cells initiate the meiotic divisions, it is imperative that they complete meiosis. Inappropriate exit from meiosis and entrance into mitosis can create polyploid cells and can lead to germline tumors. Saccharomyces cerevisiae cells enter meiosis when starved of nutrients but can return to mitosis if provided nutrient-rich medium before a defined commitment point. Once past the meiotic commitment point in prometaphase I, cells stay committed to meiosis even in the presence of a mitosis-inducing signal. Recent research investigated the maintenance of meiotic commitment in budding yeast and found that two checkpoints that do not normally function in meiosis I, the DNA damage checkpoint and the spindle position checkpoint, have crucial functions in maintaining meiotic commitment. Here, we review these findings and discuss how the mitosis-inducing signal of nutrient-rich medium could activate these two checkpoints in meiosis to prevent inappropriate meiotic exit.
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References
Agarwal R, Tang Z, Yu H, Cohen-Fix O (2003) Two distinct pathways for inhibiting pds1 ubiquitination in response to DNA damage. J Biol Chem 278:45027–45033. https://doi.org/10.1074/jbc.M306783200
Attner MA, Amon A (2012) Control of the mitotic exit network during meiosis. Mol Biol Cell 23:3122–3132. https://doi.org/10.1091/mbc.E12-03-0235
Ballew O, Lacefield S (2019) The DNA damage checkpoint and the spindle position checkpoint maintain meiotic commitment in Saccharomyces cerevisiae. Curr Biol CB 29(449–460):e442. https://doi.org/10.1016/j.cub.2018.12.043
Botchkarev VV Jr, Haber JE (2018) Functions and regulation of the polo-like kinase Cdc5 in the absence and presence of DNA damage. Curr Genet 64:87–96. https://doi.org/10.1007/s00294-017-0727-2
Broach JR (2012) Nutritional control of growth and development in yeast. Genetics 192:73–105. https://doi.org/10.1534/genetics.111.135731
Cartagena-Lirola H, Guerini I, Manfrini N, Lucchini G, Longhese MP (2008) Role of the Saccharomyces cerevisiae Rad53 checkpoint kinase in signaling double-strand breaks during the meiotic cell cycle. Mol Cell Biol 28:4480–4493. https://doi.org/10.1128/MCB.00375-08
Chan LY, Amon A (2010) Spindle position is coordinated with cell-cycle progression through establishment of mitotic exit-activating and -inhibitory zones. Mol Cell 39:444–454. https://doi.org/10.1016/j.molcel.2010.07.032
Cohen-Fix O, Koshland D (1997) The anaphase inhibitor of Saccharomyces cerevisiae Pds1p is a target of the DNA damage checkpoint pathway. Proc Natl Acad Sci USA 94:14361–14366
Dayani Y, Simchen G, Lichten M (2011) Meiotic recombination intermediates are resolved with minimal crossover formation during return-to-growth, an analogue of the mitotic cell cycle. PLoS Genet 7:e1002083. https://doi.org/10.1371/journal.pgen.1002083
Falk JE, Chan AC, Hoffmann E, Hochwagen A (2010) A Mec1- and PP4-dependent checkpoint couples centromere pairing to meiotic recombination. Dev Cell 19:599–611. https://doi.org/10.1016/j.devcel.2010.09.006
Falk JE, Tsuchiya D, Verdaasdonk J, Lacefield S, Bloom K, Amon A (2016) Spatial signals link exit from mitosis to spindle position. Elife. https://doi.org/10.7554/eLife.14036
Friedlander G, Joseph-Strauss D, Carmi M, Zenvirth D, Simchen G, Barkai N (2006) Modulation of the transcription regulatory program in yeast cells committed to sporulation. Genome Biol 7:R20. https://doi.org/10.1186/gb-2006-7-3-r20
Ganesan AT, Holter H, Roberts C (1958) Some observations on sporulation in Saccharomyces. C R Trav Lab Carlsberg Chim 31:1–6
Gihana GM, Musser TR, Thompson O, Lacefield S (2018) Prolonged cyclin-dependent kinase inhibition results in septin perturbations during return to growth and mitosis. J Cell Biol 217:2429–2443. https://doi.org/10.1083/jcb.201708153
Hartwell LH, Weinert TA (1989) Checkpoints: controls that ensure the order of cell cycle events. Science 246:629–634
Haruki H, Nishikawa J, Laemmli UK (2008) The anchor-away technique: rapid, conditional establishment of yeast mutant phenotypes. Mol Cell 31:925–932. https://doi.org/10.1016/j.molcel.2008.07.020
Hu F, Wang Y, Liu D, Li Y, Qin J, Elledge SJ (2001) Regulation of the Bub2/Bfa1 GAP complex by Cdc5 and cell cycle checkpoints. Cell 107:655–665
Kamieniecki RJ, Liu L, Dawson DS (2005) FEAR but not MEN genes are required for exit from meiosis I. Cell Cycle 4:1093–1098
Keogh MC, Kim JA, Downey M, Fillingham J, Chowdhury D, Harrison JC, Onishi M, Datta N, Galicia S, Emili A, Lieberman J, Shen X, Buratowski S, Haber JE, Durocher D, Greenblatt JF, Krogan NJ (2006) A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature 439:497–501. https://doi.org/10.1038/nature04384
Kimble J (2011) Molecular regulation of the mitosis/meiosis decision in multicellular organisms. Cold Spring Harb Perspect Biol 3:a002683. https://doi.org/10.1101/cshperspect.a002683
Laureau R, Loeillet S, Salinas F, Bergstrom A, Legoix-Ne P, Liti G, Nicolas A (2016) Extensive recombination of a yeast diploid hybrid through meiotic reversion. PLoS Genet 12:e1005781. https://doi.org/10.1371/journal.pgen.1005781
Lee DH, Pan Y, Kanner S, Sung P, Borowiec JA, Chowdhury D (2010) A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination. Nat Struct Mol Biol 17:365–372. https://doi.org/10.1038/nsmb.1769
Lopez AL 3rd, Chen J, Joo HJ, Drake M, Shidate M, Kseib C, Arur S (2013) DAF-2 and ERK couple nutrient availability to meiotic progression during Caenorhabditis elegans oogenesis. Dev Cell 27:227–240. https://doi.org/10.1016/j.devcel.2013.09.008
Lydall D, Nikolsky Y, Bishop DK, Weinert T (1996) A meiotic recombination checkpoint controlled by mitotic checkpoint genes. Nature 383:840–843. https://doi.org/10.1038/383840a0
MacQueen AJ, Hochwagen A (2011) Checkpoint mechanisms: the puppet masters of meiotic prophase. Trends Cell Biol 21:393–400. https://doi.org/10.1016/j.tcb.2011.03.004
Nebreda AR, Ferby I (2000) Regulation of the meiotic cell cycle in oocytes. Curr Opin Cell Biol 12:666–675
Neiman AM (2011) Sporulation in the budding yeast Saccharomyces cerevisiae. Genetics 189:737–765. https://doi.org/10.1534/genetics.111.127126
Nyberg KA, Michelson RJ, Putnam CW, Weinert TA (2002) Toward maintaining the genome: DNA damage and replication checkpoints. Annu Rev Genet 36:617–656. https://doi.org/10.1146/annurev.genet.36.060402.113540
O’Neill BM, Szyjka SJ, Lis ET, Bailey AO, Yates JR 3rd, Aparicio OM, Romesberg FE (2007) Pph3-Psy2 is a phosphatase complex required for Rad53 dephosphorylation and replication fork restart during recovery from DNA damage. Proc Natl Acad Sci USA 104:9290–9295. https://doi.org/10.1073/pnas.0703252104
Page AW, Orr-Weaver TL (1997) Stopping and starting the meiotic cell cycle. Curr Opin Genet Dev 7:23–31
Palou G, Palou R, Zeng F, Vashisht AA, Wohlschlegel JA, Quintana DG (2015) Three different pathways prevent chromosome segregation in the presence of DNA damage or replication stress in budding yeast. PLoS Genet 11:e1005468. https://doi.org/10.1371/journal.pgen.1005468
Palou R, Palou G, Quintana DG (2017) A role for the spindle assembly checkpoint in the DNA damage response. Curr Genet 63:275–280. https://doi.org/10.1007/s00294-016-0634-y
Sanchez Y, Bachant J, Wang H, Hu F, Liu D, Tetzlaff M, Elledge SJ (1999) Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms. Science 286:1166–1171
Scarfone I, Piatti S (2015) Coupling spindle position with mitotic exit in budding yeast: the multifaceted role of the small GTPase Tem1. Small GTPases 6:196–201. https://doi.org/10.1080/21541248.2015.1109023
Searle JS, Schollaert KL, Wilkins BJ, Sanchez Y (2004) The DNA damage checkpoint and PKA pathways converge on APC substrates and Cdc20 to regulate mitotic progression. Nat Cell Biol 6:138–145. https://doi.org/10.1038/ncb1092
Searle JS, Wood MD, Kaur M, Tobin DV, Sanchez Y (2011) Proteins in the nutrient-sensing and DNA damage checkpoint pathways cooperate to restrain mitotic progression following DNA damage. PLoS Genet 7:e1002176. https://doi.org/10.1371/journal.pgen.1002176
Sherman F, Roman H (1963) Evidence for two types of allelic recombination in yeast. Genetics 48:255–261
Simchen G, Pinon R, Salts Y (1972) Sporulation in Saccharomyces cerevisiae: premeiotic DNA synthesis, readiness and commitment. Exp Cell Res 75:207–218
Simpson-Lavy KJ, Bronstein A, Kupiec M, Johnston M (2015) Cross-Talk between carbon metabolism and the DNA damage response in S. cerevisiae. Cell Rep 12:1865–1875. https://doi.org/10.1016/j.celrep.2015.08.025
Subramanian VV, Hochwagen A (2014) The meiotic checkpoint network: step-by-step through meiotic prophase. Cold Spring Harb Perspect Biol 6:a016675. https://doi.org/10.1101/cshperspect.a016675
Tsubouchi H, Argunhan B, Tsubouchi T (2018) Exiting prophase I: no clear boundary. Curr Genet 64:423–427. https://doi.org/10.1007/s00294-017-0771-y
Tsuchiya D, Lacefield S (2013) Cdk1 modulation ensures the coordination of cell-cycle events during the switch from meiotic prophase to mitosis. Curr Biol CB 23:1505–1513. https://doi.org/10.1016/j.cub.2013.06.031
Tsuchiya D, Yang Y, Lacefield S (2014) Positive feedback of NDT80 expression ensures irreversible meiotic commitment in budding yeast. PLoS Genet 10:e1004398. https://doi.org/10.1371/journal.pgen.1004398
Wang H, Liu D, Wang Y, Qin J, Elledge SJ (2001) Pds1 phosphorylation in response to DNA damage is essential for its DNA damage checkpoint function. Genes Dev 15:1361–1372. https://doi.org/10.1101/gad.893201
Weinert TA, Kiser GL, Hartwell LH (1994) Mitotic checkpoint genes in budding yeast and the dependence of mitosis on DNA replication and repair. Genes Dev 8:652–665
Winter E (2012) The Sum1/Ndt80 transcriptional switch and commitment to meiosis in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 76:1–15. https://doi.org/10.1128/MMBR.05010-11
Zhao X, Muller EG, Rothstein R (1998) A suppressor of two essential checkpoint genes identifies a novel protein that negatively affects dNTP pools. Mol Cell 2:329–340
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This work was supported by National Institutes of Health Grant GM105755.
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Ballew, O., Lacefield, S. The DNA damage checkpoint and the spindle position checkpoint: guardians of meiotic commitment. Curr Genet 65, 1135–1140 (2019). https://doi.org/10.1007/s00294-019-00981-z
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DOI: https://doi.org/10.1007/s00294-019-00981-z