A novel motif of Rad51 serves as an interaction hub for recombination auxiliary factors

Homologous recombination (HR) is essential for maintaining genome stability. Although Rad51 is the key protein that drives HR, multiple auxiliary factors interact with Rad51 to potentiate its activity. Here, we present an interdisciplinary characterization of the interactions between Rad51 and these factors. Through structural analysis, we identified an evolutionarily conserved acidic patch of Rad51. The neutralization of this patch completely abolished recombinational DNA repair due to defects in the recruitment of Rad51 to DNA damage sites. This acidic patch was found to be important for the interaction with Rad55-Rad57 and essential for the interaction with Rad52. Furthermore, biochemical reconstitutions demonstrated that neutralization of this acidic patch also impaired the interaction with Rad54, indicating that a single motif is important for the interaction with multiple auxiliary factors. We propose that this patch is a fundamental motif that facilitates interactions with auxiliary factors and is therefore essential for recombinational DNA repair.

Automated summary

The study identified a conserved acidic patch on Rad51 that plays a crucial role in homologous recombination, as neutralization of this patch leads to defects in DNA repair and impairs interactions with auxiliary factors. This acidic patch is essential for the recruitment of Rad51, its interaction with Rad55-Rad57 and Rad52, as well as for the interaction with Rad54, highlighting its importance in recombinational DNA repair.