The DNA-binding subunit p140 of replication factor C is upregulated in cycling cells and associates with G 1 phase cell cycle regulatory proteins

To investigate the means by which a cell regulates the progression of the mitotic cell cycle, we characterized cdc44, a mutation that causes Saccharomyces cerevisiae cells to arrest before mitosis. CDC44 encodes a 96-kDa basic protein with significant homology to a human protein that binds DNA (PO-GA) and to three subunits of human replication factor C (also called activator 1). The hypothesis that Cdc44p is involved in DNA metabolism is supported by the observations that (i) levels of mitotic recombination suggest elevated rates of DNA damage in cdc44 mutants and (ii) the cell cycle arrest observed in cdc44 mutants is alleviated by the DNA damage checkpoint mutations rad9, mec1, and mec2. The predicted amino acid sequence of Cdc44p contains GTPase consensus sites, and mutations in these regions cause a conditional cell cycle arrest. Taken together, these observations suggest that the essential CDC44 gene may encode the large subunit of yeast replication factor C.

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CDC44: a putative nucleotide-binding protein required for cell cycle progression that has homology to subunits of replication factor C

Molecular and Cellular Biology ◽

10.1128/mcb.14.1.255-267.1994 ◽

1994 ◽

Vol 14 (1) ◽

pp. 255-267

Author(s):

E A Howell ◽

M A McAlear ◽

D Rose ◽

C Holm

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Cycle Arrest ◽

Large Subunit ◽

Mitotic Cell ◽

Predicted Amino Acid Sequence ◽

Replication Factor C ◽

Replication Factor ◽

Cycle Arrest ◽

Factor C

To investigate the means by which a cell regulates the progression of the mitotic cell cycle, we characterized cdc44, a mutation that causes Saccharomyces cerevisiae cells to arrest before mitosis. CDC44 encodes a 96-kDa basic protein with significant homology to a human protein that binds DNA (PO-GA) and to three subunits of human replication factor C (also called activator 1). The hypothesis that Cdc44p is involved in DNA metabolism is supported by the observations that (i) levels of mitotic recombination suggest elevated rates of DNA damage in cdc44 mutants and (ii) the cell cycle arrest observed in cdc44 mutants is alleviated by the DNA damage checkpoint mutations rad9, mec1, and mec2. The predicted amino acid sequence of Cdc44p contains GTPase consensus sites, and mutations in these regions cause a conditional cell cycle arrest. Taken together, these observations suggest that the essential CDC44 gene may encode the large subunit of yeast replication factor C.

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Cell Cycle-dependent Phosphorylation of the Large Subunit of Replication Factor C (RF-C) Leads to Its Dissociation from the RF-C Complex

Journal of Biological Chemistry ◽

10.1074/jbc.m309349200 ◽

2003 ◽

Vol 278 (48) ◽

pp. 48467-48473 ◽

Cited By ~ 4

Author(s):

Anil Munshi ◽

Dominique Cannella ◽

Howard Brickner ◽

Isabelle Salles-Passador ◽

Vladimir Podust ◽

...

Keyword(s):

Cell Cycle ◽

Large Subunit ◽

Replication Factor C ◽

Replication Factor ◽

C Complex ◽

Cycle Dependent ◽

Factor C

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Linchpin DNA-binding residues serve as go/no-go controls in the replication factor C-catalyzed clamp-loading mechanism

Journal of Biological Chemistry ◽

10.1074/jbc.m117.798702 ◽

2017 ◽

Vol 292 (38) ◽

pp. 15892-15906 ◽

Cited By ~ 1

Author(s):

Juan Liu ◽

Yayan Zhou ◽

Manju M. Hingorani

Keyword(s):

Dna Binding ◽

Replication Factor C ◽

Replication Factor ◽

Clamp Loading ◽

Binding Residues ◽

Factor C

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The Replication Factor C Clamp Loader Requires Arginine Finger Sensors to Drive DNA Binding and Proliferating Cell Nuclear Antigen Loading

Journal of Biological Chemistry ◽

10.1074/jbc.m606090200 ◽

2006 ◽

Vol 281 (46) ◽

pp. 35531-35543 ◽

Cited By ~ 47

Author(s):

Aaron Johnson ◽

Nina Y. Yao ◽

Gregory D. Bowman ◽

John Kuriyan ◽

Mike O'Donnell

Keyword(s):

Dna Binding ◽

Proliferating Cell Nuclear Antigen ◽

Nuclear Antigen ◽

Replication Factor C ◽

Clamp Loader ◽

Replication Factor ◽

Factor C ◽

Arginine Finger ◽

Proliferating Cell

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Exploration of Prognostic Biomarkers among Replication Factor C Family in the Hepatocellular Carcinoma

Evolutionary Bioinformatics ◽

10.1177/1176934321994109 ◽

2021 ◽

Vol 17 ◽

pp. 117693432199410

Author(s):

Jianxiong Deng ◽

Fangyan Zhong ◽

Weiguo Gu ◽

Feng Qiu

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Cycle ◽

Transcription Factors ◽

Mrna Expression ◽

Genetic Alterations ◽

Differentially Expressed ◽

Prognostic Biomarkers ◽

Replication Factor C ◽

Replication Factor ◽

Factor C

Hepatocellular carcinoma (HCC) is one of the common cancers with a high incidence and mortality. The human replication factor C (RFC) family contains 5 subunits that play an important role in DNA replication and DNA damage repair. RFCs are abnormally expressed in a variety of cancers; some of them are differentially expressed in HCC tissues and related to tumor growth. However, the expression, prognostic value, and effect targets of the whole RFC family in HCC are still unclear. To address these issues, we performed a multidimensional analysis of RFCs in HCC patients by Oncomine, UALCAN, GEPIA, Human protein atlas, Kaplan-Meier plotter, cBioPortal, GeneMANIA, String, and LinkedOmics. mRNA expression of RFCs was significantly increased in HCC tissues. There was a significant correlation between the expression of RFC2/3/4/5 and tumor stage of HCC patients. Besides, high mRNA expression of RFC2/4 was associated with worse overall survival (OS). Moreover, genetic alterations of RFCs were associated with worse OS in HCC patients. We found that genes co-expressed with RFC2/4 were mainly involved in biological processes, such as chromosome segregation, mitotic cell cycle phase transition, and telomere organization and they activated the cell cycle and spliceosome pathways. The gene set is mainly enriched in cancer-related kinases AURKA, ATR, CDK1, PLK1, and CHEK1. E2F family members were the key transcription factors for RFCs. Our results suggest that differentially expressed RFC2 and RFC4 are potential prognostic biomarkers in HCC and may act on E2F transcription factors and some kinase targets to dysregulate the cell cycle pathway. These efforts may provide new research directions for prognostic biomarkers and therapeutic targets in HCC.

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