RAD51C-XRCC3 complex regulates FANCM-mediated R-loop resolution to safeguard genome integrity

Fanconi anemia (FA) is characterized by bone marrow failure, congenital abnormalities, and cancer predisposition. Mutations in RAD51 paralogs have been identified in FA-like disorders and cancers. Although the role of RAD51 paralogs is well established in homologous recombination (HR)-mediated DNA repair, little is known about their role during replication stress responses. Here, we report that the RAD51C-XRCC3 (CX3) complex of RAD51 paralogs participates in the FA-pathway of R-loop tolerance mechanism. CX3 complex suppresses R-loops, transcription-replication collisions (TRC), and associated genome instability in physiological and replication stress conditions. Mechanistically, the CX3 complex physically interacts with FANCM and facilitates its recruitment to the R-loop sites to promote its resolution. Notably, cells expressing RAD51C R258H pathological mutant exhibit defective interaction with FANCM and display inefficient R-loop processing. Strikingly, the R-loop resolution function ..., , , # Data from: RAD51C-XRCC3 complex regulates FANCM-mediated R-loop resolution to safeguard genome integrity

Dataset DOI: [10.5061/dryad.mw6m9069c](https://doi.org/10.5061/dryad.mw6m9069c)

## Description of the data and file structure

All the data, including representative microscopic images, Western blot images, quantification Excel files, and AlphaFold3 structural data, are included in the submitted files.

**File Structure:**\
Organized by Figures and Analysis

Fig. 1

\|- 1A

\|- |- 1A data images/ excel file/ blot pdf

\|- 1B

...

### Files and variables

**Data processing method:**

For S9.6 quantification experiments: Raw nuclear signal intensities for S9.6 were obtained from images of around > 80 cells per sample using ImageJ software. DAPI signal was used as a mask to get nuclear boundary. The mean intensity value for the control sample was calculated. Intensity of all nuclei from all the samples were divided by the mean intensity of the control sample to obtain the \"relative...