Preventing double stand break repairs through linker histone H1x
More effective radiotherapy and chemotherapy The potential to develop a new group of more effective anti cancer drugs with fewer side effects
DNA double-strand breaks (DSB) are the most lethal form of DNA damage, since the continuity of genetic information is disrupted in both strands. The defects in DSB repair lead to accumulation of mutations resulting in developmental defects and cancer. In all cellular organisms DSB are repaired by evolutionary conserved pathways. Linker histones are the family of proteins that have been hypothesised to act as structural components of chromatin stabilising the DNA entry and exit points of nucleosomal core particles and maintaining the higher order chromatin structure. A critical and previously unknown role for Linker Histone H1x in DNA damage responses in mammalian cells has been identified. It has also been shown that cells defective in H1x expression (by siRNA mediated inactivation) are hypersensitive to ionising-radiation and exhibit defects in repair of DNA double-strand breaks. Inhibitors of H1x function could therefore potentially be used as a drug to either kill cancer cells directly or increase their vulnerability to radiotherapy and chemotherapy.
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