The essential minichromosome maintenance (Mcm) proteins Mcm2 through Mcm7 likely 
comprise the replicative helicase in eukaryotes. In addition to Mcm2-7, other 
subcomplexes, including one comprising Mcm4, Mcm6, and Mcm7, unwind DNA. Using 
Mcm4/6/7 as a tool, we reveal a role for nucleotide binding by Saccharomyces 
cerevisiae Mcm2 in modulating DNA binding by Mcm complexes. Previous studies 
have shown that Mcm2 inhibits DNA unwinding by Mcm4/6/7. Here, we show that 
interaction of Mcm2 and Mcm4/6/7 is not sufficient for inhibition; rather, Mcm2 
requires nucleotides for its regulatory role. An Mcm2 mutant that is defective 
for ATP hydrolysis (K549A), as well as ATP analogues, was used to show that ADP 
binding by Mcm2 is required to inhibit DNA binding and unwinding by Mcm4/6/7. 
This Mcm2-mediated regulation of Mcm4/6/7 is independent of Mcm3/5. Furthermore, 
the importance of ATP hydrolysis by Mcm2 to the regulation of the native complex 
was apparent from the altered DNA binding properties of Mcm2(KA)-7. Moreover, 
together with the finding that Mcm2(K549A) does not support yeast viability, 
these results indicate that the nucleotide-bound state of Mcm2 is critical in 
regulating the activities of Mcm4/6/7 and Mcm2-7 complexes.