Comparison: the path of DNA double-strand break repair process

Osaka, Japan - BRCA1 is a protein known for its role in hereditary breast cancer.

In a study published in Cell Reports, researchers at Osaka University found that protein phosphatase 1 (PP1) binds in the early stages of double-strand breaks and promotes repair through non-homologous end joining rather than homologous recombination.

The determination of which of these two pathways is used to repair double-strand breaks is carefully regulated by the cell in many different ways

The lead author of the study, Shin-Ya Isobe, explained: “Double-strand breaks that are not protected by the RIF1 protein complex are easily digested by other proteins, resulting in a single-stranded DNA that can be repaired by homologous recombination

To determine other factors that can help protect the newly broken DNA ends, the researchers used a technique called proteomics mass spectrometry to find out which proteins interact with RIF1

Senior author Chikashi Obuse explained: "We found that PP1 specifically binds to RIF1 at the end of the broken DNA.

Importantly, the interaction between PP1 and RIF1 helps prevent double-stranded DNA breaks from forming a single-stranded "tail", which is bound by the shield protein

"Our findings reveal a new mechanism for selecting a double-strand DNA break repair pathway that works early in the repair process," Isobe said

Given that the problem of double-strand break repair is a key feature of many cancers, knowing more about how cells decide which pathway to use to repair these damaged parts can provide important insights into the development of cancer

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"Protein Phosphatase 1 acts as a RIF1 effector to suppress DSB resection prior to Shieldin action," was published in Cell Reports at DOI: https:/ / doi.