Cdc45p Assembles into a Complex with Cdc46p/Mcm5p, is Required for Minichromosome Maintenance, and is Essential for Chromosomal DNA Replication

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1996 Oct 29

PMID 8901577

Citations 51

Authors

B Hopwood

S Dalton

Affiliations

Soon will be listed here.

Abstract

We report the isolation and characterization of CDC45, which encodes a polypeptide of 650 amino acids that is essential for the initiation of chromosomal DNA replication in the budding yeast, Saccharomyces cerevisiae. CDC45 genetically interacts with at least two members of the MCM (minichromosome maintenance) family of replication genes, CDC46 and CDC47, which are proposed to perform a role in restricting initiation of DNA replication to once per cell cycle. Like mutants in several MCM genes, alleles of CDC45 also show a severe minichromosome maintenance defect. Together, these observations imply that Cdc45p performs a role in the control of initiation events at chromosomal replication origins. We investigated this possibility further and present evidence demonstrating that Cdc45p is assembled into complexes with one MCM family member, Cdc46p/Mcm5p. These observations point to a role for Cdc45p in controlling the early steps of chromosomal DNA replication in conjunction with MCM polypeptide complexes. Unlike the MCMs, however, the subcellular localization of Cdc45p does not vary with the cell cycle, making it likely that Cdc45p interacts with MCMs only during the nuclear phase of MCM localization in G1.

Citing Articles

Validation of CDC45 as a novel biomarker for diagnosis and prognosis of gastric cancer.

Wu L, Gao G, Mi H, Luo Z, Wang Z, Liu Y PeerJ. 2024; 12:e17130.

PMID: 38515458 PMC: 10956518. DOI: 10.7717/peerj.17130.

High abundance of CDC45 inhibits cell proliferation through elevation of HSPA6.

Fu Y, Lv Z, Kong D, Fan Y, Dong B Cell Prolif. 2022; 55(7):e13257.

PMID: 35642733 PMC: 9251052. DOI: 10.1111/cpr.13257.

Karyopherin-mediated nucleocytoplasmic transport.

Wing C, Fung H, Chook Y Nat Rev Mol Cell Biol. 2022; 23(5):307-328.

PMID: 35058649 PMC: 10101760. DOI: 10.1038/s41580-021-00446-7.

Expression and prognosis of CDC45 in cervical cancer based on the GEO database.

He Z, Wang X, Yang Z, Jiang Y, Li L, Wang X PeerJ. 2021; 9:e12114.

PMID: 34557356 PMC: 8420875. DOI: 10.7717/peerj.12114.

The developing mouse coronal suture at single-cell resolution.

Farmer D, Mlcochova H, Zhou Y, Koelling N, Wang G, Ashley N Nat Commun. 2021; 12(1):4797.

PMID: 34376651 PMC: 8355337. DOI: 10.1038/s41467-021-24917-9.

References

Gibson S, Surosky R, Tye B . The phenotype of the minichromosome maintenance mutant mcm3 is characteristic of mutants defective in DNA replication. Mol Cell Biol. 1990; 10(11):5707-20. PMC: 361340. DOI: 10.1128/mcb.10.11.5707-5720.1990. View

J Blow J, Laskey R . A role for the nuclear envelope in controlling DNA replication within the cell cycle. Nature. 1988; 332(6164):546-8. DOI: 10.1038/332546a0. View

BLOCK D, Eitzman P, Wangensteen J, Srienc F . Slit scanning of Saccharomyces cerevisiae cells: quantification of asymmetric cell division and cell cycle progression in asynchronous culture. Biotechnol Prog. 1990; 6(6):504-12. DOI: 10.1021/bp00006a015. View

Yan H, Gibson S, Tye B . Mcm2 and Mcm3, two proteins important for ARS activity, are related in structure and function. Genes Dev. 1991; 5(6):944-57. DOI: 10.1101/gad.5.6.944. View

Hennessy K, Lee A, Chen E, Botstein D . A group of interacting yeast DNA replication genes. Genes Dev. 1991; 5(6):958-69. DOI: 10.1101/gad.5.6.958. View

Dingwall C, Laskey R . Nuclear targeting sequences--a consensus?. Trends Biochem Sci. 1991; 16(12):478-81. DOI: 10.1016/0968-0004(91)90184-w. View

Thommes P, Fett R, Schray B, Burkhart R, Barnes M, Kennedy C . Properties of the nuclear P1 protein, a mammalian homologue of the yeast Mcm3 replication protein. Nucleic Acids Res. 1992; 20(5):1069-74. PMC: 312092. DOI: 10.1093/nar/20.5.1069. View

Coxon A, Maundrell K, Kearsey S . Fission yeast cdc21+ belongs to a family of proteins involved in an early step of chromosome replication. Nucleic Acids Res. 1992; 20(21):5571-7. PMC: 334388. DOI: 10.1093/nar/20.21.5571. View

Yan H, Merchant A, Tye B . Cell cycle-regulated nuclear localization of MCM2 and MCM3, which are required for the initiation of DNA synthesis at chromosomal replication origins in yeast. Genes Dev. 1993; 7(11):2149-60. DOI: 10.1101/gad.7.11.2149. View

10.

Hu B, Burkhart R, Schulte D, Musahl C, Knippers R . The P1 family: a new class of nuclear mammalian proteins related to the yeast Mcm replication proteins. Nucleic Acids Res. 1993; 21(23):5289-93. PMC: 310560. DOI: 10.1093/nar/21.23.5289-a. View

11.

Miyake S, Okishio N, Samejima I, Hiraoka Y, Toda T, Saitoh I . Fission yeast genes nda1+ and nda4+, mutations of which lead to S-phase block, chromatin alteration and Ca2+ suppression, are members of the CDC46/MCM2 family. Mol Biol Cell. 1993; 4(10):1003-15. PMC: 275734. DOI: 10.1091/mbc.4.10.1003. View

12.

Dohmen R, Wu P, Varshavsky A . Heat-inducible degron: a method for constructing temperature-sensitive mutants. Science. 1994; 263(5151):1273-6. DOI: 10.1126/science.8122109. View

13.

Todorov I, Pepperkok R, Philipova R, Kearsey S, Ansorge W, Werner D . A human nuclear protein with sequence homology to a family of early S phase proteins is required for entry into S phase and for cell division. J Cell Sci. 1994; 107 ( Pt 1):253-65. DOI: 10.1242/jcs.107.1.253. View

14.

Diffley J, Cocker J, Dowell S, Rowley A . Two steps in the assembly of complexes at yeast replication origins in vivo. Cell. 1994; 78(2):303-16. DOI: 10.1016/0092-8674(94)90299-2. View

15.

Kimura H, Nozaki N, Sugimoto K . DNA polymerase alpha associated protein P1, a murine homolog of yeast MCM3, changes its intranuclear distribution during the DNA synthetic period. EMBO J. 1994; 13(18):4311-20. PMC: 395358. DOI: 10.1002/j.1460-2075.1994.tb06751.x. View

16.

Dalton S, Whitbread L . Cell cycle-regulated nuclear import and export of Cdc47, a protein essential for initiation of DNA replication in budding yeast. Proc Natl Acad Sci U S A. 1995; 92(7):2514-8. PMC: 42248. DOI: 10.1073/pnas.92.7.2514. View

17.

Kubota Y, Mimura S, Nishimoto S, Takisawa H, Nojima H . Identification of the yeast MCM3-related protein as a component of Xenopus DNA replication licensing factor. Cell. 1995; 81(4):601-9. DOI: 10.1016/0092-8674(95)90081-0. View

18.

Chong J, Mahbubani H, Khoo C, J Blow J . Purification of an MCM-containing complex as a component of the DNA replication licensing system. Nature. 1995; 375(6530):418-21. DOI: 10.1038/375418a0. View

19.

Madine M, Khoo C, Mills A, Laskey R . MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells. Nature. 1995; 375(6530):421-4. DOI: 10.1038/375421a0. View

20.

Todorov I, Attaran A, Kearsey S . BM28, a human member of the MCM2-3-5 family, is displaced from chromatin during DNA replication. J Cell Biol. 1995; 129(6):1433-45. PMC: 2291170. DOI: 10.1083/jcb.129.6.1433. View