Systematic proximal mapping of the classical RAD51 paralogs unravel functionally and clinically relevant interactors...

Area of Science:

• Molecular Biology
• Genetics
• Cancer Research

Background:

• Homologous recombination (HR) is crucial for DNA double-strand break repair and genome stability.
• RAD51 paralogs are involved in HR and replication stress response, but their precise roles remain unclear.
• Understanding RAD51 paralog functions is vital for cancer prevention.

Purpose of the Study:

• To investigate the proximal interactome of classical RAD51 paralogs in cellulo.
• To explore the interplay between RAD51 paralogs, RNA metabolism, and replication stress.
• To identify potential biomarkers for breast cancer prognosis.

Main Methods:

• BioID proximity labeling approach was used to map RAD51 paralog interactomes.
• Cells were exposed to hydroxyurea (HU) to induce replication stress.
• RNA expression analysis was performed to assess prognostic potential.

Main Results:

• Identified known RAD51 paralog sub-complexes (BCDX2, CX3) and revealed spliceosome machinery as a novel interacting component.
• Discovered significant modulation of RNA metabolic factors within RAD51 paralog proximity interactomes upon HU treatment.
• Found that several RNA pathway members correlate with poorer patient outcomes in breast cancer.

Conclusions:

• The study uncovers novel partners of RAD51 paralogs involved in genome stability maintenance.
• A crosstalk between RAD51 paralogs and RNA processing pathways during replication stress is suggested.
• Identified RAD51 paralog-associated RNA pathway factors hold potential as breast cancer biomarkers.