Zhang lab DNA Processing Machines Laboratory

various colourful protein structures

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We are trying to better understand how our DNA is opened up when it needs to be transcribed or "read," and how systems in our bodies sense and repair damaged DNA.

DNA is damaged tens of thousands of times each day in every human cell from exposure to toxic chemicals, UV and other radiation, which can lead to mutations. These mutations can lead to dysfunctional and potentially harmful outcomes. Accessing, protecting, and repairing DNA are therefore fundamental processes in cells and crucial for human health. These processes are carried out by molecular machines that are tightly orchestrated and regulated.

To understand how DNA is opened during the transcription process, we use a unique bacterial system where the aim is to capture the process at many different stages to create a sort of molecular movie.

To understand how DNA damage is sensed and repaired we are studying how a double stranded DNA break, one of the most severe types of DNA damage, is detected. We're also looking at how key pieces in the repair process are recruited and assembled, how cells coordinate other cellular events with the repair process, and how the repair is actually carried out.

We use a multi-disciplinary approach, combining different structural biology techniques and biochemical and biophysical methodologies, to provide a molecular understanding of these highly complex processes.