Cdc45p assembles into a complex with Cdc46p/Mcm5p, is required for minichromosome maintenance, and is essential for chromosomal DNA replication.

Hopwood, Blair; Dalton, Stephen

doi:10.1073/pnas.93.22.12309

Cited by 107 publications

(106 citation statements)

References 28 publications

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Section: Resultsmentioning

confidence: 99%

“…Cdc45 is involved in DNA replication and remains nuclear throughout the S. cerevisiae cell cycle (Moir et al 1982;Hopwood and Dalton 1996). Cdc45 interacts with the minichromosome maintenance proteins, which regulate DNA replication (Hopwood and Dalton 1996). Mcm10 is a constitutively nuclear chromatin-associated protein that plays a role in DNA replication initiation by recruiting both the Mcm2-7 complex and DNA polymerase-a to DNA replication origins (Burich and Lei 2003;Ricke and Bielinsky 2004;Zhu et al 2007).…”

Section: Resultsmentioning

confidence: 99%

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The Classical Nuclear Localization Signal Receptor, Importin-α, Is Required for Efficient Transition Through the G1/S Stage of the Cell Cycle inSaccharomyces cerevisiae

et al. 2009

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There is significant evidence linking nucleocytoplasmic transport to cell cycle control. The budding yeast, Saccharomyces cerevisiae, serves as an ideal model system for studying transport events critical to cell cycle progression because the nuclear envelope remains intact throughout the cell cycle. Previous studies linked the classical nuclear localization signal (cNLS) receptor, importin-a/Srp1, to the G 2 /M transition of the cell cycle. Here, we utilize two engineered mutants of importin-a/Srp1 with specific molecular defects to explore how protein import affects cell cycle progression. One mutant, Srp1-E402Q, is defective in binding to cNLS cargoes that contain two clusters of basic residues termed a bipartite cNLS. The other mutant, Srp1-55, has defects in release of cNLS cargoes into the nucleus. Consistent with distinct in vivo functional consequences for each of the Srp1 mutants analyzed, we find that overexpression of different nuclear transport factors can suppress the temperature-sensitive growth defects of each mutant. Studies aimed at understanding how each of these mutants affects cell cycle progression reveal a profound defect at the G 1 to S phase transition in both srp1-E402Q and srp1-55 mutants as well as a modest G 1 /S defect in the temperature-sensitive srp1-31 mutant, which was previously implicated in G 2 /M. We take advantage of the characterized defects in the srp1-E402Q and srp1-55 mutants to predict candidate cargo proteins likely to be affected in these mutants and provide evidence that three of these cargoes, Cdc45, Yox1, and Mcm10, are not efficiently localized to the nucleus in importin-a mutants. These results reveal that the classical nuclear protein import pathway makes important contributions to the G 1 /S cell cycle transition.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The Classical Nuclear Localization Signal Receptor, Importin-α, Is Required for Efficient Transition Through the G1/S Stage of the Cell Cycle inSaccharomyces cerevisiae

et al. 2009

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“…Evidence suggests that CDC45 may function with the MCM complex, because genetic interactions (Moir et al, 1982;Hardy, 1997;Zou et al, 1997) and biochemical interactions (Hopwood and Dalton, 1996) between the MCMs and CDC45 have been shown in yeast. More recently, CDC45 was shown to bind to Mcm2p at the G1/S transition in an S-CDKdependent manner (Zou and Stillman, 2000).…”

Section: Introductionmentioning

confidence: 99%

A CDC45 Homolog in Arabidopsis Is Essential for Meiosis, as Shown by RNA Interference–Induced Gene Silencing

et al. 2003

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CDC45 is required for the initiation of DNA replication in yeast and cell proliferation in mammals and functions as a DNA polymerase ␣ loading factor in Xenopus . We have cloned a CDC45 homolog from Arabidopsis whose expression is upregulated at the G1/S transition and in young meiotic flower buds. One-third of Arabidopsis 35S : CDC45 T1 RNA interference lines are partially to completely sterile, and the proportion of sterile plants is increased by using a dmc1 promoter. T1 plants have decreased levels of the CDC45 transcript and contain 21-to 23-bp RNA fragments specific to the CDC45 gene. T2 transgenic lines, in which small RNA fragments are still present, were used to analyze S-phase entry by 5-bromodeoxyuridine incorporation, which was not altered compared with that in the wild type. However, microarray data show that other cell cycle genes are upregulated or downregulated. T2 plants also have highly reduced fertility. The severity of the phenotype is correlated with the levels of the CDC45 transcript and small RNA fragments. Severe chromosome fragmentation arising during meiosis, which is not the result of a defect in the repair of SPO11-induced double strand breaks, leads to abnormal chromosome segregation and defective pollen and ovule development.

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“…CDC45 is an essential gene for the initiation of DNA replication in Saccharomyces cerevisiae [41][42][43]. A human homologue of CDC45 has been isolated, and the encoded protein has been shown to associate with human origin recognition c o m p l e x ( O R C ) p r o t e i n [ 4 4 ] o r h u m a n minichromosome maintenance protein (MCM) and a subunit of DNA polymerase α [45] in cultured cells.…”

Section: Transcription Factors Involved In Icm Differentiationmentioning

confidence: 99%

Pre-Implantation Conceptus and Maternal Uterine Communications: Molecular Events Leading to Successful Implantation

Imakawa

Chang

Christenson

2004

Journal of Reproduction and Development

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Abstract. Implantation, a critical step for mammals in establishing pregnancy, requires successful completion of sequential events such as maternal uterine development, conceptus development and attachment, and placental formation. To reach the stage of placental formation, synchronized development of the conceptus and uterus throughout the implantation period is absolutely required. A number of factors expressed at the uterine endometrium and/or conceptus, which are associated with peri-implantation development, have been identified. In addition to a temporal and spatial expression of these factors, their roles in intra-and inter-cellular interactions make it difficult to fully understand physiological roles played during the critical period. This paper focuses on early conceptus development, maternal preparation for implantation and uterine-conceptus communication during the pre-implantation period, rather than the subsequent events such as conceptus attachment to the maternal endometrium. New aspects of pre-implantation processes are evaluated through simultaneous expressions of transcription factors as they possibly regulate the complex processes of implantation events in murine species and ruminant ungulates.

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Cdc45p assembles into a complex with Cdc46p/Mcm5p, is required for minichromosome maintenance, and is essential for chromosomal DNA replication.

Cited by 107 publications

References 28 publications

The Classical Nuclear Localization Signal Receptor, Importin-α, Is Required for Efficient Transition Through the G1/S Stage of the Cell Cycle inSaccharomyces cerevisiae

The Classical Nuclear Localization Signal Receptor, Importin-α, Is Required for Efficient Transition Through the G1/S Stage of the Cell Cycle inSaccharomyces cerevisiae

A CDC45 Homolog in Arabidopsis Is Essential for Meiosis, as Shown by RNA Interference–Induced Gene Silencing

Pre-Implantation Conceptus and Maternal Uterine Communications: Molecular Events Leading to Successful Implantation

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