Human CDT1 associates with CDC7 and recruits CDC45 to chromatin during S phase.
The initiation of DNA replication is a tightly controlled process that involves the formation of distinct complexes at origins of DNA replication at specific periods of the cell cycle. Pre-replicative complexes are formed during telophase and early G(1). They rearrange at the start of S phase to form pre-initiation complexes, which are a prerequisite for DNA replication. The CDT1 protein is required for the formation of the pre-replicative complexes. Here we show that human CDT1 associates with the CDC7 kinase and recruits CDC45 to chromatin. Moreover, we show that the amount of CDT1 bound to chromatin is regulated by CDC7. We propose a model in which chromatin-bound CDT1 is first stabilized and subsequently displaced by CDC7 activity, thereby ensuring the timely execution of DNA replication.
Ballabeni
Andrea
A
Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, Milan 20135, Italy.
Zamponi
Raffaella
R
Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, Milan 20135, Italy.
Caprara
Greta
G
Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, Milan 20135, Italy.
Melixetian
Marina
M
Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, Milan 20135, Italy.
Bossi
Sergio
S
Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, Milan 20135, Italy.
Masiero
Laura
L
Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, Milan 20135, Italy.
Helin
Kristian
K
Department of Experimental Oncology, European Institute of Oncology, Via Adamello 16, Milan 20135, Italy; Biotech Research & Innovation Centre (BRIC), University of Copenhagen, Copenhagen 2200, Denmark; Centre for Epigenetics, University of Copenhagen, Copenhagen 2200, Denmark. Electronic address: kristian.helin@bric.dk.
D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism*; D004261:DNA Replication; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016196:S Phase
C113571:CDC45 protein, human; C467199:CDT1 protein, human; D018797:Cell Cycle Proteins; D002843:Chromatin; C068619:CDC7 protein, human; D017346:Protein Serine-Threonine Kinases