Human DNA helicase B interacts with the replication initiation protein Cdc45 and facilitates Cdc45 binding onto chromatin.
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.
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: jeannine.gerhardt@gmail.com.
Jeannine
J
Gerhardt
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA.
Gulfem D
GD
Guler
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235, USA.
Ellen
E
Fanning
D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D004265:DNA Helicases / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D006801:Humans
C113571:CDC45 protein, human; D018797:Cell Cycle Proteins; D002843:Chromatin; C484263:HELB protein, human; D004265:DNA Helicases
Cdc45; DNA replication initiation; Human DNA Helicase B