protein coding gene - cdc18 (SPBC14C8.07c) - MCM loader

Gene summary

Standard name

cdc18

Systematic ID

SPBC14C8.07c

Product

MCM loader

Organism

Schizosaccharomyces pombe (fission yeast)

UniProt ID

P41411

ORFeome ID

40/40F10

Characterisation status

biological role published

Feature type

mRNA gene

Genomic location

chromosome II: 2215955..2217984 reverse strand

Annotation

Protein features

Orthologs

• CDC6 (HGNC:1744) Homo sapiens
• cdc18 (SJAG_02074) Schizosaccharomyces japonicus
• CDC6 (YJL194W) Saccharomyces cerevisiae

References / Literature

GO_REF:0000108 - Automatic assignment of GO terms using logical inference, based on on inter-ontology links.

PMID:10388806 - Rereplication phenomenon in fission yeast requires MCM proteins and other S phase genes.

Snaith HA et al. Genetics 1999 Jul;152(3):839-51

PMID:10747035 - Chromatin binding of the fission yeast replication factor mcm4 occurs during anaphase and requires ORC and cdc18.

Kearsey SE et al. EMBO J 2000 Apr 03;19(7):1681-90

PMID:10209119 - F-box/WD-repeat proteins pop1p and Sud1p/Pop2p form complexes that bind and direct the proteolysis of cdc18p.

Wolf DA et al. Curr Biol 1999 Apr 08;9(7):373-6

PMID:20473289 - Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe.

Kim DU et al. Nat Biotechnol 2010 Jun;28(6):617-623

PMID:24763107 - Absolute proteome and phosphoproteome dynamics during the cell cycle of Schizosaccharomyces pombe (Fission Yeast).

Carpy A et al. Mol Cell Proteomics 2014 Aug;13(8):1925-36

PMID:25720772 - Quantitative phosphoproteomics reveals pathways for coordination of cell growth and division by the conserved fission yeast kinase pom1.

Kettenbach AN et al. Mol Cell Proteomics 2015 May;14(5):1275-87

PMID:28223353 - Sap1 is a replication-initiation factor essential for the assembly of pre-replicative complex in the fission yeast Schizosaccharomyces pombe .

Guan L et al. J Biol Chem 2017 Apr 14;292(15):6056-6075

PMID:32355220 - DNA replication machinery prevents Rad52-dependent single-strand annealing that leads to gross chromosomal rearrangements at centromeres.

Onaka AT et al. Commun Biol 2020 Apr 30;3(1):202

PMID:12186947 - A novel chk1-dependent G1/M checkpoint in fission yeast.

Synnes M et al. J Cell Sci 2002 Sep 15;115(Pt 18):3609-18

PMID:30134042 - The INO80 complex activates the transcription of S-phase genes in a cell cycle-regulated manner.

Knezevic I et al. FEBS J 2018 Oct;285(20):3870-3881

PMID:21971174 - Abundance of prereplicative complexes (Pre-RCs) facilitates recombinational repair under replication stress in fission yeast.

Maki K et al. J Biol Chem 2011 Dec 02;286(48):41701-41710

PMID:22681890 - Hierarchical modularity and the evolution of genetic interactomes across species.

Ryan CJ et al. Mol Cell 2012 Jun 08;46(5):691-704

PMID:7916658 - The fission yeast cdc18+ gene product couples S phase to START and mitosis.

Kelly TJ et al. Cell 1993 Jul 30;74(2):371-82

PMID:8643672 - cdc18+ regulates initiation of DNA replication in Schizosaccharomyces pombe.

Muzi Falconi M et al. Proc Natl Acad Sci U S A 1996 Feb 20;93(4):1566-70

PMID:9755169 - Cdc18 transcription and proteolysis couple S phase to passage through mitosis.

Baum B et al. EMBO J 1998 Oct 01;17(19):5689-98

PMID:11514535 - Autophosphorylation of archaeal Cdc6 homologues is regulated by DNA.

Grabowski B et al. J Bacteriol 2001 Sep;183(18):5459-64

PMID:21511999 - Comparative functional genomics of the fission yeasts.

Rhind N et al. Science 2011 May 20;332(6032):930-6

PMID:10766248 - The Cdt1 protein is required to license DNA for replication in fission yeast.

Nishitani H et al. Nature 2000 Apr 06;404(6778):625-8

PMID:20736315 - Specific replication origins promote DNA amplification in fission yeast.

Kiang L et al. J Cell Sci 2010 Sep 15;123(Pt 18):3047-51

PMID:11606752 - Redundant control of rereplication in fission yeast.

Gopalakrishnan V et al. Proc Natl Acad Sci U S A 2001 Nov 06;98(23):13114-9

PMID:22144913 - Widespread cotranslational formation of protein complexes.

Duncan CD et al. PLoS Genet 2011 Dec;7(12):e1002398

PMID:14648198 - DSC1-MCB regulation of meiotic transcription in Schizosaccharomyces pombe.

Cunliffe L et al. Mol Genet Genomics 2004 Feb;271(1):60-71

PMID:8552194 - Interaction of Cdc2 and Cdc18 with a fission yeast ORC2-like protein.

Leatherwood J et al. Nature 1996 Jan 25;379(6563):360-3

PMID:8887552 - A novel S phase inhibitor in fission yeast.

Woollard A et al. EMBO J 1996 Sep 02;15(17):4603-12

PMID:9436991 - Negative regulation of Cdc18 DNA replication protein by Cdc2.

Lopez-Girona A et al. Mol Biol Cell 1998 Jan;9(1):63-73

PMID:9928931 - The S/M checkpoint at 37 degrees C and the recovery of viability of the mutant poldeltats3 require the crb2+/rhp9+ gene in fission yeast.

Grenon M et al. Mol Gen Genet 1999 Jan;260(6):522-34

PMID:15302827 - The forkhead transcription factor Fkh2 regulates the cell division cycle of Schizosaccharomyces pombe.

Bulmer R et al. Eukaryot Cell 2004 Aug;3(4):944-54

PMID:8598285 - Rum1 and Cdc18 link inhibition of cyclin-dependent kinase to the initiation of DNA replication in Schizosaccharomyces pombe.

Jallepalli PV et al. Genes Dev 1996 Mar 01;10(5):541-52

PMID:16371652 - Production of reactive oxygen species in response to replication stress and inappropriate mitosis in fission yeast.

Marchetti MA et al. J Cell Sci 2006 Jan 01;119(Pt 1):124-31

PMID:9034336 - Fission yeast pheromone blocks S-phase by inhibiting the G1 cyclin B-p34cdc2 kinase.

Stern B et al. EMBO J 1997 Feb 03;16(3):534-44

PMID:30824696 - Systematic analysis reveals the prevalence and principles of bypassable gene essentiality.

Li J et al. Nat Commun 2019 Mar 01;10(1):1002

PMID:8521469 - p65cdc18 plays a major role controlling the initiation of DNA replication in fission yeast.

Nishitani H et al. Cell 1995 Nov 03;83(3):397-405

GO_REF:0000111 - Gene Ontology annotations Inferred by Curator (IC) using at least one Inferred by Sequence Similarity (ISS) annotation to support the inference

PMID:28903048 - Set2 Methyltransferase Facilitates DNA Replication and Promotes Genotoxic Stress Responses through MBF-Dependent Transcription.

Pai CC et al. Cell Rep 2017 Sep 12;20(11):2693-2705

PMID:16899242 - Analysis of Mcm2-7 chromatin binding during anaphase and in the transition to quiescence in fission yeast.

Namdar M et al. Exp Cell Res 2006 Oct 15;312(17):3360-9

PMID:11988741 - Maintenance of replication forks and the S-phase checkpoint by Cdc18p and Orp1p.

Murakami H et al. Nat Cell Biol 2002 May;4(5):384-8

PMID:17531813 - Cdc18 enforces long-term maintenance of the S phase checkpoint by anchoring the Rad3-Rad26 complex to chromatin.

Hermand D et al. Mol Cell 2007 May 25;26(4):553-63

PMID:35157728 - TOR complex 2 contributes to regulation of gene expression via inhibiting Gcn5 recruitment to subtelomeric and DNA replication stress genes.

Cohen A et al. PLoS Genet 2022 Feb;18(2):e1010061

PMID:10725227 - A fission yeast general translation factor reveals links between protein synthesis and cell cycle controls.

Grallert B et al. J Cell Sci 2000 Apr;113 ( Pt 8):1447-58

PMID:31719112 - Checkpoint Regulation of Nuclear Tos4 Defines S Phase Arrest in Fission Yeast.

Kim SM et al. G3 (Bethesda) 2020 Jan 07;10(1):255-266

PMID:11030343 - Structure and function of Cdc6/Cdc18: implications for origin recognition and checkpoint control.

Liu J et al. Mol Cell 2000 Sep;6(3):637-48

PMID:10589835 - Budding yeast Cdc6p induces re-replication in fission yeast by inhibition of SCF(Pop)-mediated proteolysis.

Wolf DA et al. Mol Gen Genet 1999 Oct;262(3):473-80

PMID:11532929 - Expression of Cdc18/Cdc6 and Cdt1 during G2 phase induces initiation of DNA replication.

Yanow SK et al. EMBO J 2001 Sep 03;20(17):4648-56

PMID:18154680 - Checkpoint effects and telomere amplification during DNA re-replication in fission yeast.

Mickle KL et al. BMC Mol Biol 2007 Dec 21;8:119

PMID:15507118 - An interactive gene network for securin-separase, condensin, cohesin, Dis1/Mtc1 and histones constructed by mass transformation.

Yuasa T et al. Genes Cells 2004 Nov;9(11):1069-82

PMID:10888871 - Mitotic replication initiation proteins are not required for pre-meiotic S phase.

Forsburg SL et al. Nat Genet 2000 Jul;25(3):263-8

PMID:23173672 - Identification of novel genes involved in DNA damage response by screening a genome-wide Schizosaccharomyces pombe deletion library.

Pan X et al. BMC Genomics 2012 Nov 23;13:662

PMID:14970237 - Requirement of the SCFPop1/Pop2 Ubiquitin Ligase for Degradation of the Fission Yeast S Phase Cyclin Cig2.

Yamano H et al. J Biol Chem 2004 Apr 30;279(18):18974-80

PMID:17112379 - The CENP-B homolog, Abp1, interacts with the initiation protein Cdc23 (MCM10) and is required for efficient DNA replication in fission yeast.

Locovei AM et al. Cell Div 2006 Nov 17;1:27

PMID:11486016 - Control of DNA rereplication via Cdc2 phosphorylation sites in the origin recognition complex.

Vas A et al. Mol Cell Biol 2001 Sep;21(17):5767-77

PMID:11781565 - Feedback regulation of the MBF transcription factor by cyclin Cig2.

Ayté J et al. Nat Cell Biol 2001 Dec;3(12):1043-50

PMID:12419251 - Stable association of mitotic cyclin B/Cdc2 to replication origins prevents endoreduplication.

Wuarin J et al. Cell 2002 Nov 01;111(3):419-31

PMID:40015273 - A comprehensive Schizosaccharomyces pombe atlas of physical transcription factor interactions with proteins and chromatin.

Skribbe M et al. Mol Cell 2025 Feb 19;

PMID:11937031 - CDK phosphorylation of Drc1 regulates DNA replication in fission yeast.

Noguchi E et al. Curr Biol 2002 Apr 02;12(7):599-605

PMID:6943408 - Cell division cycle mutants altered in DNA replication and mitosis in the fission yeast Schizosaccharomyces pombe.

Nasmyth K et al. Mol Gen Genet 1981;182(1):119-24

PMID:9177184 - Interaction of the S phase regulator cdc18 with cyclin-dependent kinase in fission yeast.

Brown GW et al. Proc Natl Acad Sci U S A 1997 Jun 10;94(12):6142-7

PMID:7957098 - Fission yeast cut5 links nuclear chromatin and M phase regulator in the replication checkpoint control.

Saka Y et al. EMBO J 1994 Nov 15;13(22):5319-29

PMID:8895665 - The ORC1 homolog orp1 in fission yeast plays a key role in regulating onset of S phase.

Grallert B et al. Genes Dev 1996 Oct 15;10(20):2644-54

PMID:9739083 - Cdc18p can block mitosis by two independent mechanisms.

Greenwood E et al. J Cell Sci 1998 Oct;111 ( Pt 20):3101-8

PMID:39476757 - Characterization of Ksg1 protein kinase-dependent phosphoproteome in the fission yeast S. pombe.

Cipak L et al. Biochem Biophys Res Commun 2024 Oct 25;736:150895

PMID:9353247 - Regulation of the replication initiator protein p65cdc18 by CDK phosphorylation.

Jallepalli PV et al. Genes Dev 1997 Nov 01;11(21):2767-79

PMID:1934126 - Common genes and pathways in the regulation of the mitotic and meiotic cell cycles of Schizosaccharomyces pombe.

Grallert B et al. Curr Genet 1991 Aug;20(3):199-204

PMID:10101168 - The role of nucleotide binding and hydrolysis in the function of the fission yeast cdc18(+) gene product.

DeRyckere D et al. Genetics 1999 Apr;151(4):1445-57

PMID:12960401 - Intra-G1 arrest in response to UV irradiation in fission yeast.

Nilssen EA et al. Proc Natl Acad Sci U S A 2003 Sep 16;100(19):10758-63

PMID:23697806 - A genome-wide resource of cell cycle and cell shape genes of fission yeast.

Hayles J et al. Open Biol 2013 May 22;3(5):130053

PMID:31260531 - Gcn5-mediated acetylation at MBF-regulated promoters induces the G1/S transcriptional wave.

González-Medina A et al. Nucleic Acids Res 2019 Sep 19;47(16):8439-8451

GO_REF:0000024 - Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity.

PMID:25533348 - Tolerance of deregulated G1/S transcription depends on critical G1/S regulon genes to prevent catastrophic genome instability.

Caetano C et al. Cell Rep 2014 Dec 24;9(6):2279-89

PMID:10381393 - Functionally homologous DNA replication genes in fission and budding yeast.

Sánchez M et al. J Cell Sci 1999 Jul;112 ( Pt 14):2381-90

PMID:12535531 - A cell cycle-regulated GATA factor promotes centromeric localization of CENP-A in fission yeast.

Chen ES et al. Mol Cell 2003 Jan;11(1):175-87

PMID:12604790 - The Cdc23 (Mcm10) protein is required for the phosphorylation of minichromosome maintenance complex by the Dfp1-Hsk1 kinase.

Lee JK et al. Proc Natl Acad Sci U S A 2003 Mar 04;100(5):2334-9

PMID:7739540 - The Schizosaccharomyces pombe MBF complex requires heterodimerization for entry into S phase.

Ayté J et al. Mol Cell Biol 1995 May;15(5):2589-99

PMID:23101633 - Quantitative analysis of fission yeast transcriptomes and proteomes in proliferating and quiescent cells.

Marguerat S et al. Cell 2012 Oct 26;151(3):671-83

PMID:17690116 - Cdc18/CDC6 activates the Rad3-dependent checkpoint in the fission yeast.

Fersht N et al. Nucleic Acids Res 2007;35(16):5323-37

PMID:9693370 - Mutational effect of fission yeast polalpha on cell cycle events.

Bhaumik D et al. Mol Biol Cell 1998 Aug;9(8):2107-23

PMID:11359920 - Regulation of initiation of S phase, replication checkpoint signaling, and maintenance of mitotic chromosome structures during S phase by Hsk1 kinase in the fission yeast.

Takeda T et al. Mol Biol Cell 2001 May;12(5):1257-74

PMID:21712547 - Mitotic substrates of the kinase aurora with roles in chromatin regulation identified through quantitative phosphoproteomics of fission yeast.

Koch A et al. Sci Signal 2011 Jun 28;4(179):rs6

PMID:9990507 - Two F-box/WD-repeat proteins Pop1 and Pop2 form hetero- and homo-complexes together with cullin-1 in the fission yeast SCF (Skp1-Cullin-1-F-box) ubiquitin ligase.

Kominami K et al. Genes Cells 1998 Nov;3(11):721-35

PMID:7700230 - DNA polymerase delta is required for the replication feedback control of cell cycle progression in Schizosaccharomyces pombe.

Francesconi S et al. Mol Gen Genet 1995 Mar 10;246(5):561-9

PMID:21239883 - S. pombe replication protein Cdc18 (Cdc6) interacts with Swi6 (HP1) heterochromatin protein: region specific effects and replication timing in the centromere.

Li PC et al. Cell Cycle 2011 Jan 15;10(2):323-36

PMID:37970674 - SUMOylation regulates Lem2 function in centromere clustering and silencing.

Strachan J et al. J Cell Sci 2023 Dec 01;136(23)

PMID:24006488 - The DNA damage and the DNA replication checkpoints converge at the MBF transcription factor.

Ivanova T et al. Mol Biol Cell 2013 Nov;24(21):3350-7

PMID:19714215 - The fission yeast homeodomain protein Yox1p binds to MBF and confines MBF-dependent cell-cycle transcription to G1-S via negative feedback.

Aligianni S et al. PLoS Genet 2009 Aug;5(8):e1000626

PMID:9203581 - Fission yeast WD-repeat protein pop1 regulates genome ploidy through ubiquitin-proteasome-mediated degradation of the CDK inhibitor Rum1 and the S-phase initiator Cdc18.

Kominami K et al. Genes Dev 1997 Jun 15;11(12):1548-60

PMID:33313903 - Ribosome profiling reveals ribosome stalling on tryptophan codons and ribosome queuing upon oxidative stress in fission yeast.

Rubio A et al. Nucleic Acids Res 2021 Jan 11;49(1):383-399

PMID:9383050 - Mutational analysis of Cdc19p, a Schizosaccharomyces pombe MCM protein.

Forsburg SL et al. Genetics 1997 Nov;147(3):1025-41

PMID:9653157 - sud1(+) targets cyclin-dependent kinase-phosphorylated Cdc18 and Rum1 proteins for degradation and stops unwanted diploidization in fission yeast.

Jallepalli PV et al. Proc Natl Acad Sci U S A 1998 Jul 07;95(14):8159-64

PMID:11850415 - Purification and characterization of the Schizosaccharomyces pombe origin recognition complex: interaction with origin DNA and Cdc18 protein.

Chuang RY et al. J Biol Chem 2002 May 10;277(19):16920-7

PMID:30635289 - Cell Cycle-Regulated Transcription of CENP-A by the MBF Complex Ensures Optimal Level of CENP-A for Centromere Formation.

Aristizabal-Corrales D et al. Genetics 2019 Mar;211(3):861-875

PMID:26912660 - Gad8 Protein Is Found in the Nucleus Where It Interacts with the MluI Cell Cycle Box-binding Factor (MBF) Transcriptional Complex to Regulate the Response to DNA Replication Stress.

Cohen A et al. J Biol Chem 2016 Apr 22;291(17):9371-81

PMID:9303312 - Control of S-phase periodic transcription in the fission yeast mitotic cycle.

Baum B et al. EMBO J 1997 Aug 01;16(15):4676-88

PMID:12161753 - The transcriptional program of meiosis and sporulation in fission yeast.

Mata J et al. Nat Genet 2002 Sep;32(1):143-7

GO_REF:0000002 - Comments

PMID:15278909 - The regulation of competence to replicate in meiosis by Cdc6 is conserved during evolution.

Lemaître JM et al. Mol Reprod Dev 2004 Sep;69(1):94-100

PMID:18667534 - Activation of the DNA damage checkpoint in mutants defective in DNA replication initiation.

Yin L et al. Mol Biol Cell 2008 Oct;19(10):4374-82

PMID:10490657 - Association of fission yeast Orp1 and Mcm6 proteins with chromosomal replication origins.

Ogawa Y et al. Mol Cell Biol 1999 Oct;19(10):7228-36

PMID:27298342 - Identification of S-phase DNA damage-response targets in fission yeast reveals conservation of damage-response networks.

Willis NA et al. Proc Natl Acad Sci U S A 2016 Jun 28;113(26):E3676-85

PMID:9679144 - Regulation of cell polarity by microtubules in fission yeast.

Sawin KE et al. J Cell Biol 1998 Jul 27;142(2):457-71

PMID:29996109 - Quantitative Phosphoproteomics Reveals the Signaling Dynamics of Cell-Cycle Kinases in the Fission Yeast Schizosaccharomyces pombe.

Swaffer MP et al. Cell Rep 2018 Jul 10;24(2):503-514

PB_REF:0000006 - Disease associations from Monarch via human-pombe orthologs