Understanding how the skin cancer virus outcompetes host cell replication

Known as licensed DNA replication, this controlled process occurs only once each time a cell divides. In contrast, when a virus hijacks a host cell’s DNA replication machinery, it replicates hundreds of times.

This “unlicensed” replication is not subject to the same quality control and is much more prone to errors. With MCV, certain mutations can cause the virus’s entire genetic code, or genome, to get inserted into its host’s genome, causing previously normal cells to undergo uninhibited growth and division to become cancerous. the team found that MCV’s version of helicase does not form sleeves around the DNA as they had expected. Instead, it directly pries apart the DNA molecule. The viral helicase can do this repeatedly without using ATP, enabling the virus to outcompete normal cellular replication.

Reference: Unlicensed origin DNA melting by MCV and SV40 polyomavirus LT proteins is independent of ATP-dependent helicase activity, Proceedings of the National Academy of Sciences, DOI 10.1073/pnas.2308010120