53BP1 and BRCA1 antibodies used in important new breast cancer study - By: Ronald Kresten

We at Novus Biologicals have a broad antibody catalogue devoted to both DNA repair and cancer research. A recent mouse study, conducted by Andre Nussenzweig of the National Cancer Institute, showed that mutations in the murine BRCA1 gene could be compensated by deletion of the secondary gene P53-binding protein 1 (53BP1), lessening the likelihood of breast cancer.

53BP1 antibodies have been used in a number of cancer studies, showing that the P53-binding protein 1 plays a significant role in suppression of tumour development. It phosphorylates and relocalises at the sites of DNA damage, in particular, double-strand breaks, showing a probable role in DNA repair. However, when mutations of the BRCA1 gene occur, 53BP1can actually increase the risk of tumour development.

The Brca1 protein also plays an important role in DNA repair, via homologous recombination (HR). This is used to repair replication-associated chromosome breaks, a type of DNA damage that occurs spontaneously when cells divide. If HR is made defective through Brca1 mutation, alternative DNA repair pathways are found – for example, that associated with 53BP1. However, this pathway is more mutagenic than HR, increasing the risk of tumour development.

Human BRCA1 mutations are known to increase the risk of breast and other cancers developing. Nussenzweig’s study used a strain of defective BRCA1 mice, which caused development of mammary tumours similar to those seen in humans. It was noted that when the mice also carried a defective 53BP1 gene, tumour development was greatly suppressed. In addition, 53BP1 inactivation led to restoration of the DNA repair mechanism lost when BRAC1 was mutated.

Nussenzweig performed a series of antibody assays on cultured Brca-deficient cells, proving it was possible to restore homologous recombination by inactivating 53BP1. The antibody studies also threw new light on the interaction of the Brca1 and 53BP1 pathways, opening up new possibilities for breast cancer therapy.

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