DNA replication in eukaryotes requires nucleosome disruption ahead of the 
replication fork and reassembly behind. An unresolved issue concerns how histone 
dynamics are coordinated with fork progression to maintain chromosomal 
stability. Here, we characterize a complex in which the human histone chaperone 
Asf1 and MCM2-7, the putative replicative helicase, are connected through a 
histone H3-H4 bridge. Depletion of Asf1 by RNA interference impedes DNA 
unwinding at replication sites, and similar defects arise from overproduction of 
new histone H3-H4 that compromises Asf1 function. These data link Asf1 chaperone 
function, histone supply, and replicative unwinding of DNA in chromatin. We 
propose that Asf1, as a histone acceptor and donor, handles parental and new 
histones at the replication fork via an Asf1-(H3-H4)-MCM2-7 intermediate and 
thus provides a means to fine-tune replication fork progression and histone 
supply and demand.