Sae2 controls Mre11 endo- and exonuclease activities by different mechanisms
Institutional Communication Service
28 August 2024
A paper published in the journal “Nature Communications” by the Sugimoto, Shinohara and Cejka laboratories shows how Sae2 regulates the nuclease activity of the MRX complex to initiate Homologous Recombination mediated repair of DNA breaks.
DNA double-strand breaks (DSBs) are a threat for genome integrity and cell survival and must be repaired correctly. Key to this process is the Mre11-Rad50-Xrs2 complex (MRX), which collaborates with Sae2 to initiate DSB repair. Using a mix of genetic and biochemical approaches, the authors identify a mutant of the Rad50, K1299R, that helps shed light on how Sae2 regulates the endonuclease and 3’-5’ exonuclease activities of the MRX complex. In particular, the mutant is defective in the Sae2-dependent MRX 3’-5’ exonuclease activity, but not In the endonuclease activity, suggesting that Sae2 controls the two activities in distinct ways. Additionally, the authors uncover how the exonuclease activity of MRX is required for the processing of Spo11-mediated breaks during meiosis but is dispensable during the removal of hairpin structures. This work was a collaboration between Giordano Reginato from the Cejka laboratory at IRB, and the Sugimoto (New Jersey Medical School, Newark, USA) and Shinoara (Kindai University, Osaka, Japan) teams.
Link to the Scientific Article: https://www.nature.com/articles/s41467-024-51493-5
