BRCA1, BRCA2 and DNA repair mechanisms

Researcher: Dr Andrew Blackford

Location: University of Oxford

Dates:  Sept 2018 – Sept 2022*     Status: In Progress

Funding: £75,000

Research Theme: Therapies

*1 year extension due to COVID

Aims

As part of ABC’s Junior Research Fellowship programme launched in 2018, Dr Andrew Blackford is the first recipient of the funding. He aims to further understand which regions of the BRCA1 and BRCA2 proteins are essential for repairing DNA damage and preventing tumour formation.

Background

Cancer is mainly a genetic disease caused by changes (mutations), that build up over time in our cells’ DNA. Damage to our DNA happens all the time, but our cells have repair mechanisms to fix this.

One repair mechanism is called ‘DNA double-stranded break repair’. BRCA1 and BRCA2 are two proteins that play a critical role in this process, but scientists do not understand exactly how these proteins repair DNA at the molecular level.

Certain regions in the BRCA1 and BRCA2 proteins are thought to be important for stopping tumours forming and Dr Blackford’s research hopes to better understand the function of these ‘short, linear peptide motifs’. His research may also help to explain why patients who inherit faulty BRCA1 and BRCA2 genes are more predisposed to breast cancer.

Potential benefit for patients

Some of the most effective cancer treatments work by causing DNA damage and this research aims to increase our understanding of the DNA damage repair mechanism at the molecular level. This in turn may help to improve existing treatments as well as develop new ones for breast cancer.

Publications

The Bloom syndrome complex senses RPA-coated single-stranded DNA to restart stalled replication forks. Ann-Marie K. Shorrocks, Samuel E. Jones, Kaima Tsukada, Carl A. Morrow, Zoulikha Belblidia, Johanna Shen, Iolanda Vendrell, Roman Fischer, Benedikt M. Kessler & Andrew N. Blackford. Nat Commun. 2021 Jan 26;12(1):585 (validation of analysis methods).