Influence of the human cohesion establishment factor Ctf4/AND-1 on DNA replication Journal Article
| Authors: | Bermudez, V. P.; Farina, A.; Tappin, I.; Hurwitz, J. |
| Article Title: | Influence of the human cohesion establishment factor Ctf4/AND-1 on DNA replication |
| Abstract: | Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion. In this report, we examined the mechanism of action of human Ctf4 (hCtf4) in DNA replication both in vitro and in vivo. Our findings show that the purified hCtf4 exists as a dimer and that the hCtf4 SepB domain likely plays a primary role determining the dimeric structure. hCtf4 binds preferentially to DNA template-primer structures, interacts directly with the replicative DNA polymerases (α, δ, and ε), and markedly stimulates the polymerase activities of DNA polymerases α and ε in vitro. Depletion of hCtf4 in HeLa cells by small interfering RNA resulted in G1/S phase arrest. DNA fiber analysis revealed that cells depleted of hCtf4 exhibited a rate of DNA replication slower than cells treated with control small interfering RNA. These findings suggest that in human cells, hCtf4 plays an essential role in DNA replication and its ability to stimulate the replicative DNA polymerases may contribute to this effect. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | controlled study; unclassified drug; dna binding protein; human cell; dna-binding proteins; nonhuman; flow cytometry; methodology; dna polymerase; dna replication; protein domain; protein function; animal cell; animal; metabolism; animals; cell cycle; cell cycle s phase; genes; protein depletion; small interfering rna; protein binding; rna, small interfering; transcription factor; in vivo study; enzyme activation; in vitro study; enzyme activity; hela cell; hela cells; structure activity relation; physiology; transcription factors; rna; gene expression regulation; chemistry; dna; protein purification; cell cycle arrest; sister chromatid exchange; dimerization; dna replications; in-vitro; cell cycle g1 phase; human cells; protein dna interaction; adhesion; s-phase; mechanism of action; dimeric structure; dna fiber; dna-template; gene products; polymerase activities; polymers; acidic nucleoplasmic dna binding protein 1; dna directed dna polymerase alpha; dna directed dna polymerase delta; dna directed dna polymerase epsilon; and 1 protein, human; and-1 protein, human; dna directed dna polymerase beta; dna template; insect; dna polymerase i; insects |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 285 |
| Issue: | 13 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2010-03-26 |
| Start Page: | 9493 |
| End Page: | 9505 |
| Language: | English |
| DOI: | 10.1074/jbc.M109.093609 |
| PUBMED: | 20089864 |
| PROVIDER: | scopus |
| PMCID: | PMC2843200 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: JBCHA" - "Source: Scopus" |
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