Structure of the Smc5-6 DNA repair and chromosome maintenance protein complex

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The accurate inheritance of the genetic material (DNA) is key to the survival of all organisms. DNA has to be copied (replicated) before cells divide but obstacles such as damaged DNA bases can lead to problems during the copying process. Cells have developed different ways to remove such obstacles (repair), and if the DNA damage cannot be removed it can be bypassed, either during or immediately after DNA copying (tolerance). Failure of repair or tolerance can result in errors when the DNA is copied. These errors cause permanent genetic changes, which in turn can result in increased cancer incidence. Many proteins are involved in repair and tolerance. One of these, Smc5-6, which we have been studying for several years, is a big ?protein complex? with eight components. We propose to combine the expertise of our four research groups to determine the 3-dimensional structure of this complex. This will enable us to understand how the different components fit together, what they each do, and how they help to fulfil the functions of the protein complex in the cell. This will help us to understand how Smc6 acts to protect us from the problems caused by DNA damage during DNA copying. This work has implications for the development of cancer and aging in the general population.