A Cancer Gene Switch For Repairing Damaged DNA

Main Category: Ovarian Cancer
Also Included In: Cancer / Oncology;  Breast Cancer;  Genetics
Article Date: 27 May 2009 - 0:00 PDT

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Scientists at the Medical Research Council Laboratory of Molecular Biology uncover how an important cancer gene, BRCA1, works by increasing the accuracy with which broken DNA is repaired. Women who inherit a faulty version of the BRCA1 gene are at a higher risk of developing breast or ovarian cancer.

In a research paper appearing in Nature on 21 May, Dr Kevin Hiom and Dr Maximina H. Yun from the Cambridge laboratory describe how an important cancer gene, BRCA1, works by increasing the accuracy with which broken DNA is repaired and thus reducing the risk of cancers developing.

Mutations in the BRCA1 gene are associated with a significant increase in breast cancer risk and with the onset of ovarian cancer. By studying the interaction between BRCA1 and a protein called CtIP, the scientists discovered a switch that causes DNA breaks to be repaired using another identical piece of DNA as a template. Using the template makes sure the correct genetic sequence is restored without mistakes, thereby reducing the chance of introducing harmful mutations.

Lead author Dr Hiom said:
"Our findings help us to understand of how breaks in DNA strands can be repaired in a way that preserves our genetic code so that harmful mutations, which may lead to cancer, are kept to a minimum. We use chicken cells because they repair their DNA in a similar way to humans. Also we can easily create cells lacking different factors involved in DNA repair to study in the laboratory what happens when these factors are missing."

"Up to now, it was unclear how this accurate mechanism for repairing DNA breaks is turned on so we are very pleased with the result."

Cancer is caused by alterations in the sequence of the genetic material DNA. These mutations often arise when DNA becomes damaged, for example, through the generation of DNA breaks. Sometimes this damage is repaired accurately to restore the original DNA sequence and other times it is repaired inaccurately to produce a mutation.

Together BRCA1 and CtIP act on broken ends to enable the reconstitution of one strand of a DNA helix to generate a region of single-stranded DNA. The generation of this single stranded DNA tail, which becomes the template for repair, is a critical step in the initiation of accurate DNA repair.

By promoting the interaction of BRCA1 with CtIP it might be possible to increase the levels of accurate DNA repair and reduce the frequency of cancer causing mutations.

Source
Medical Research Council