MedWire News: Mediator of Rap80 Interactions and Targeting 40 kD (MERIT40) is a Rap80-associated protein that is essential for BRCA1–Rap80 complex protein interactions, stability, and targeting of DNA double-strand breaks (DSBs), study findings show.

BRCA1 is a key protein in the mechanism of DNA repair of replication errors by the DNA damage response (DDR) system. Inactivating mutations in BRCA1 results in deficient repair of DSBs. Previous studies have shown that the BRCA1– Rap80 complex plays a major role in these processes; however, the mechanisms involved have remained unclear.

To investigate, Roger Greenberg (University of Pennsylvania School of Medicine, Philadelphia, USA) and colleagues conducted a series of in vitro and in vivo biochemical and histochemical studies.

Their results, published in the journal Genes & Development, identify a new protein termed MERIT40 and provide “molecular insights into how BRCA1 associates with independently assembled core protein complexes to maintain genome integrity.”

Importantly, they show that MERIT40 only interacts with wild-type BRCA1 and not with a cancer-causing BRCA1 mutant.

The results suggest that “MERIT40 contributes an essential component of the Rap80 complex for BRCA1 DSB recognition,” the team reports.

They add that MERIT40 may act as a scaffold for the BRCA1–Rap80 complex “by maintaining the interactions, stability, and DSB targeting for each component.”

The authors conclude that “given the central importance of BRCA1 in genome integrity control and tumor suppression, these findings raise the possibility that MERIT40, like other essential BRCA1-associated factors, may be worthy of investigation as a target of disease-causing mutations.”

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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