Newly discovered DNA repair mechanism offers potential therapeutic targets for cancer and neurodegenerative diseases

The tightly-coiled DNA in almost every human cell is subjected to thousands of insults and injuries from both inside and outside every day, which is why the human body has evolved multiple efficient mechanisms to repair DNA damage

"We have delicate mechanisms for repairing DNA breaks, and when those mechanisms fail, we end up with disease

DNA damage repair is a double-edged sword: when it goes wrong, it can lead to diseases, such as cancer and degenerative movement disorders, but it can also be used to treat a variety of cancers using drugs that interfere with the ability of DNA to repair itself, resulting in Cancer cells stop replicating and die

Mostoslavsky explained that previous studies of DNA repair mechanisms have been carried out using protein purification systems developed by biochemists, but these systems have relatively low yields, or "throughputs

"We decided to develop a high-throughput assay to try to identify repair factors in a more unbiased way

With the help of co-investigators at the National Cancer Institute of Madrid and other research centers in the United States, Canada and China, Mostoslavsky and his colleagues at MGH and Harvard have developed a highly sensitive method to Visualize the working of DNA repair mechanisms

They describe their technique -- a combination of high-throughput microscopy and machine learning -- in the journal Cell Reports

The researchers first developed a high-throughput microscopy test to analyze how proteins attract or repel double-stranded DNA breaks

They then conducted a proof-of-principle study in which the researchers found that a specific factor labeled PHF20 was excluded from the site of DNA damage because it interfered with the recruitment of another key DNA repair factor labeled 53BP1

For example, the system developed by Mostoslavsky and colleagues could help improve the treatment of breast and ovarian cancers caused by mutations in the susceptibility genes BRCA1 and BRCA2

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