Structural basis of self-loading by replicative helicases

Abstract

DNA replication is conserved in all forms of life on earth, from subcellular structures such as viruses to human cells. Here we study a group of virus parasites whose replication is initiated by helicases like those found in simian viruses and eukaryotic cells. The process by which these viral helicases initiate the replication of the DNA remains poorly understood. Here, we show how the helicase binds the parasite’s origin of replication with its carboxy terminal domains (CTDs) adopting flexible and different conformations. The CTD’s flexibility moves the DNA towards the inside of the helicase’s ring and bends the DNA at three discrete positions curving it. Our cryo-EM snapshots show that the helicase deforms the DNA while self-loading onto it as the first stage of the initiation of DNA replication, suggesting that initial melting and self-loading are coupled processes in this type of virus parasites.