BRCA1-BARD1 exhibits a dual functionality in DNA repair and replication stress response, which is influenced by the presence and concentration of RAD51. The potential mechanisms for this switch include:
Concentration-Dependent Binding: At low concentrations, RAD51 may promote the pro-nuclease function of BRCA1-BARD1, facilitating DNA end resection necessary for homologous recombination. However, as RAD51 concentration increases, it may bind to BRCA1-BARD1, altering its conformation and shifting its role towards DNA protection.
Competitive Inhibition: RAD51, as a recombinase, can compete with nucleases for binding to BRCA1-BARD1. When RAD51 is abundant, it may inhibit the access of nucleases to the DNA, thereby preventing degradation and promoting the stabilization of replication forks during stress conditions.
Regulatory Feedback Mechanisms: The presence of RAD51 may trigger signaling pathways that modify the activity of BRCA1-BARD1. For instance, post-translational modifications such as phosphorylation could be influenced by RAD51 binding, leading to a change in the functional state of BRCA1-BARD1 from a pro-nuclease to a protective role.
Contextual Influence: The cellular context, including the type of DNA damage and the phase of the cell cycle, may also dictate the functional outcome of BRCA1-BARD1. In scenarios where replication stress is high, the protective function may be prioritized to safeguard genomic integrity, while in the presence of DSBs, the pro-nuclease function may be favored.