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Human DNA Helicase B Interacts with the Replication Initiation Protein Cdc45 and Facilitates Cdc45 Binding Onto Chromatin

Overview
Journal Exp Cell Res
Specialty Cell Biology
Date 2015 May 3
PMID 25933514
Citations 12
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Abstract

The chromosomal DNA replication in eukaryotic cells begins at replication initation sites, which are marked by the assembly of the pre-replication complexes in early G1. At the G1/S transition, recruitment of additional replication initiation proteins enables origin DNA unwinding and loading of DNA polymerases. We found that depletion of the human DNA helicase B (HDHB) inhibits the initiation of DNA replication, suggesting a role of HDHB in the beginning of the DNA synthesis. To gain insight into the function of HDHB during replication initiation, we examined the physical interactions of purified recombinant HDHB with key initiation proteins. HDHB interacts directly with two initiation factors TopBP1 and Cdc45. In addition we found that both, the N-terminus and helicase domain of HDHB bind to the N-terminus of Cdc45. Furthermore depletion of HDHB from human cells diminishes Cdc45 association with chromatin, suggesting that HDHB may facilitate Cdc45 recruitment at G1/S in human cells.

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References
1.
Moyer S, Lewis P, Botchan M . Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase. Proc Natl Acad Sci U S A. 2006; 103(27):10236-10241. PMC: 1482467. DOI: 10.1073/pnas.0602400103. View

2.
Gerhardt J, Jafar S, Spindler M, Ott E, Schepers A . Identification of new human origins of DNA replication by an origin-trapping assay. Mol Cell Biol. 2006; 26(20):7731-46. PMC: 1636883. DOI: 10.1128/MCB.01392-06. View

3.
Masai H, Taniyama C, Ogino K, Matsui E, Kakusho N, Matsumoto S . Phosphorylation of MCM4 by Cdc7 kinase facilitates its interaction with Cdc45 on the chromatin. J Biol Chem. 2006; 281(51):39249-61. DOI: 10.1074/jbc.M608935200. View

4.
Gray S, Gerhardt J, Doerfler W, Small L, Fanning E . An origin of DNA replication in the promoter region of the human fragile X mental retardation (FMR1) gene. Mol Cell Biol. 2006; 27(2):426-37. PMC: 1800797. DOI: 10.1128/MCB.01382-06. View

5.
Kumagai A, Shevchenko A, Shevchenko A, Dunphy W . Treslin collaborates with TopBP1 in triggering the initiation of DNA replication. Cell. 2010; 140(3):349-59. PMC: 2857569. DOI: 10.1016/j.cell.2009.12.049. View