Hi Chris

Love your show on Five Live. I have a question thats been puzzling me recently. At the molecular level how does mutation occur in the gene? How does say exposure to radiation cause a point mutation on the chromosome?



Louise - This month's question is being answered by Dr. Philip Zegerman from the Gurdon Institute in Cambridge. Kashefa Farooqi emailed us to ask, "At the molecular level, how does mutation occur in the genome and how does exposure to radiation for example cause a point in mutation in the

Philip - And so, our genome is really just a long organic molecule of repeating units which are called bases and it's the order and composition of these bases that really determines your genome, what your genes do. And if you do get changes to the base composition or the organisation of these As, Cs, Gs, and Ts, that's a process that's called mutation. So this polymer, this organic polymer that is your genome is actually sensitive to damage by chemicals or high energy radiation. What UV does, for example, is it causes these bases that your genome is made out of to stick together really in a process that's crosslinking. And x-rays have sufficient energy that actually make your DNA helix, your double helix to actually cause it to break. So it can actually cause the backbone of the DNA to be nicked or broken, and these are called strand breaks. I've told you that the genome is essentially a long string of bases, 3.2 billion of them in the case of humans, but the important point is that every cell in the body has a perfect copy of your genome which means that every time your cell divides, it has to make a perfect copy of this 3.2 million bases. This essentially involves a process where your DNA is duplicated by a special group of enzymes which are called DNA polymerases. And these polymerases travel along your DNA, copying it as faithfully as they can, but if they hit a problem, for example, a strand break, a lesion or perhaps two bases that have been stuck together by UV light, then your DNA polymerases can't replicate very well, and they have a high propensity to cause errors.

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