MCM2 is a subunit of the replicative helicase machinery shown to interact with 
histones H3 and H4 during the replication process through its N-terminal domain. 
During replication, this interaction has been proposed to assist disassembly and 
assembly of nucleosomes on DNA. However, how this interaction participates in 
crosstalk with histone chaperones at the replication fork remains to be 
elucidated. Here, we solved the crystal structure of the ternary complex between 
the histone-binding domain of Mcm2 and the histones H3-H4 at 2.9 Å resolution. 
Histones H3 and H4 assemble as a tetramer in the crystal structure, but MCM2 
interacts only with a single molecule of H3-H4. The latter interaction exploits 
binding surfaces that contact either DNA or H2B when H3-H4 dimers are 
incorporated in the nucleosome core particle. Upon binding of the ternary 
complex with the histone chaperone ASF1, the histone tetramer dissociates and 
both MCM2 and ASF1 interact simultaneously with the histones forming a 1:1:1:1 
heteromeric complex. Thermodynamic analysis of the quaternary complex together 
with structural modeling support that ASF1 and MCM2 could form a chaperoning 
module for histones H3 and H4 protecting them from promiscuous interactions. 
This suggests an additional function for MCM2 outside its helicase function as a 
proper histone chaperone connected to the replication pathway.