DNA unwinding via minichromosome maintenance

Minichromosome maintenance (MCM) proteins play an essential role in DNA unwinding and are completely conserved throughout eukaryotic and archaeal cells, underscoring their fundamental importance in DNA replication. Biochemists have characterized some of the protein motifs that affect the unwinding of DNA by MCM proteins. Elizabeth Jenkinson and James Chong studied how changes in the MCM proteins of a methanogenic archaeon affected DNA replication. The authors found that amino acid substitutions in the MCM protein affected ATP hydrolysis, DNA binding, and duplex unwinding. A single amino acid change in the N terminus or a deletion of a 72-aa sequence in the C terminus disrupted the movement of an internal helix that controls DNA binding and unwinding. Jenkinson and Chong also deleted the internal helix, which completely stopped DNA unwinding. However, this change also sped up ATP hydrolysis, showing that the wild-type MCM protein may not be working at peak efficiency. These results provide insights into MCM proteins’ helicase activity and control of the DNA binding and unwinding process. — P.D.