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Two current undergraduate students have contributed to a research paper published recently in the highly-regarded journal Science. MBChB Medicine and Surgery students Nick Campion and Suzanne Herron studied for an intercalated degree in Medical Science, during which time they worked on research into the replication mechanisms behind DNA.

Research project leader, Dr Aga Gambus explains more about the research:

“We all have about 2m of DNA in every one of our cells. Every time cells in our body want to divide they need to first duplicate their genome - their DNA. When Watson and Crick described the structure of DNA in the 1950s they suggested also how it could be duplicated; the double helix can be unwound and new strands can be synthesised in a complementary manner, so that the process is semiconservative (new double strand is made of one new and one old strand). Ever since their discovery scientists have tried to describe how this process works in detail, as its perfect execution is essential to maintain genomic stability and prevent cancer formation.

“We know that one of the main causes of mutations that lead to cancer development is unrepaired mistakes that arise during the process of duplication. Thus, a lot of work had been done towards understanding the synthesis of DNA and, within the last 15 years, the initiation stage of DNA replication. However, very little is known about how this process finishes, which is the subject of this paper.

“The study shows a first glimpse of the mechanism that unloads the replication machinery at the end of the process. The replication machinery (replisome) is formed of about 150 proteins and built around a few key organising centres. One of them is a replicative helicase, which is the protein complex that can unwind double stranded DNA to open it to create the templates for DNA synthesis. The helicases are loaded onto DNA in hundreds of thousands, and about 30,000-50,000 of them are activated per cell during DNA replication. They then go through DNA, unwinding it, until they meet a helicase coming from the opposite direction. These helicases, once working, are very precious as if they get taken off DNA by mistake they cannot be put back on. This means however that at the end, when they do meet each other they have to be removed by a sophisticated mechanism.

“We have shown in our work that one of the components of this helicase (Mcm7 subunit) is modified at the final stage of replication by attachment of a small protein modifier called ubiquitin. This modification allows it to be recognised by a protein remodeler, which then removes it from the DNA allowing the whole process to complete.”

The breakthrough discovery has been described by one expert reviewers as "a landmark in the DNA replication field".

Polyubiquitylation drives replisome disassembly at the termination of DNA replication. Moreno SP, Bailey R, Campion N, Herron S, Gambus A. Science. 2014 Oct 24;346(6208):477-81.