many factors required for chromosomal dna replication have been identified in unicellular eukaryotes . however , dna replication in complex multicellular organisms is poorly understood . here , we report the identification of gemc1 , a novel vertebrate protein required for chromosomal dna replication . 
 gemc1 is highly conserved in vertebrates and is preferentially expressed in proliferating cells . using xenopus 
 egg extract we show that xenopus gemc1 ( xgemc1 ) binds to checkpoint and replication factor topbp1 , which promotes xgemc1 binding to chromatin during pre - replication complex ( pre - rc ) formation . 
 we demonstrate that xgemc1 directly interacts with replication factors such as cdc45 and cdk2-cycline by which it is heavily phosphorylated . 
 phosphorylated xgemc1 stimulates initiation of dna replication whereas depletion of xgemc1 prevents dna replication onset due to impairment of cdc45 loading onto chromatin . 
 likewise , inhibition of gemc1 expression by morpholino and sirna oligos prevents dna replication in embryonic and somatic vertebrate cells . 
 these data suggest that gemc1 promotes initiation of chromosomal dna replication in higher eukaryotes by mediating topbp1 and cdk2 dependent recruitment of cdc45 onto replication origins .