Research sheds light on cell's DNA repair kit
Spanish researchers have identified how some cancer cells are able to resist chemotherapy, raising hope of new strategies to make cancerous tumours more vulnerable to treatment. The study, which was lead by Dr Jordi Surrallés of the Autonomous University of Barcelona and funded in part by the EU, is published in the EMBO (European Molecular Biology Organisation) Journal. When a mutation arises in humans, one of the main pathways responsible for repairing the damage is the cancer-suppressing Fanconi anaemia/BRCA pathway which helps cells identify genetic mutations and so prevent the development of cancers. Breakdowns in this pathway are implicated in a number of cancers. However, at the same time the pathway is also involved in helping tumours resist chemotherapy. Many chemotherapy drugs kill tumour cells by inducing genetic mutations, and sometimes the Fanconi anaemia/BRCA proteins accidentally help the tumour by identifying these mutations and repairing them. Understanding how the 13 genes involved in the pathway work is therefore of great interest to cancer researchers. In this latest study, the researchers have worked out exactly how the Fanconi anaemia proteins detect the presence of mutations. They found that mutations in the DNA block the process of DNA replication, a process which is vital if cells are to be able to divide and proliferate. Blocking the DNA replication process activates an enzyme called ATR kinase, which adds phosphate groups to the proteins surrounding the damaged DNA. These phosphate groups act like a flag, indicating the location of the genetic damage to the Fanconi proteins. The researchers hope their work will make it possible to devise strategies to make cancer cells more sensitive to chemotherapy. Dr Surallés' team has observed that when the creation of one of the Fanconi genes is partially inhibited, breast cancer cell lines are two to three times more sensitive to chemotherapy.
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