Retraction: The structure of SV40 large T hexameric helicase in complex with AT-rich origin DNA

When a cell divides to form a new cell, it must also copy its DNA. An important step for starting DNA replication is to break or “melt” the bonds between the two strands of DNA that make up the double helix. This happens at a specific site on the DNA called the replication origin, and allows double-stranded DNA to partially unwind into two single strands. Each strand acts as a template to form a new copy of its partner strand. In many organisms, ring-shaped proteins called helicases attach directly to double-stranded DNA to melt the bonds at the replication origin. Viruses also have helicases that they can use to hijack the cell’s replication machinery and get it to copy the viral DNA. One such helicase called Large T antigen is an important part of a tumor virus called simian virus 40. Large T has a ‘hexameric’ structure, similar to the cell’s own helicases, and researchers often use it as a model for studying the replication process. However, key questions remain. How do hexameric helicases interact with the double-stranded DNA replication origin? And what are the molecular mechanisms by which these helicases melt bonds in double-stranded DNA? Gai et al. used a technique called X-ray crystallography to examine the molecular structure of the Large T helicase when it is attached to DNA. The resulting structures show that six subunits of Large T helicase assemble a ring around the replication origin, each making unique bonds with the DNA. The helicase ring squeezes the DNA, partially breaking the bonds between the DNA strands and causing local melting of the DNA. With the understanding of how the Large T hexamer helicase interacts with its DNA replication origin and how its assembly initiates DNA melting, the future challenge is to explain the process by which the partially melted origin opens up fully for replication to begin.