# EYA-1 is required for genomic integrity independent of H2AX signalling in Caenorhabditis elegans

## TL;DR

This study shows that the EYA-1 protein in worms is crucial for maintaining genomic integrity, even without H2AX signaling.

## Contribution

The study reveals a novel role for EYA-1 in DNA repair independent of H2AX in C. elegans.

## Key findings

- EYA-1 absence causes abnormal chromosome morphology in C. elegans embryos.
- EYA-1 mutants are highly sensitive to DNA damage but less affected by DNA replication stress.
- Loss of EYA-1 leads to a mortal germline and sterility in worms.

## Abstract

Resolving genomic insults is essential for the survival of any species. In the case of eukaryotes, several pathways comprise the DNA damage repair network, and many components have high evolutionary conservation. These pathways ensure that DNA damage is resolved which prevents disease associated mutations from occurring in a de novo manner. In this study, we investigated the role of the Eyes Absent (EYA) homologue in Caenorhabditis elegans and its role in DNA damage repair. Current understanding of mammalian EYA1 suggests that EYA1 is recruited in response to H2AX signalling to dsDNA breaks. C. elegans do not possess a H2AX homologue, although they do possess homologues of the core DNA damage repair proteins. Due to this, we aimed to determine if eya-1 contributes to DNA damage repair independent of H2AX.

We used a putative null mutant for eya-1 in C. elegans and observed that absence of eya-1 results in abnormal chromosome morphology in anaphase embryos, including chromosomal bridges, missegregated chromosomes, and embryos with abnormal nuclei. Additionally, inducing different types of genomic insults, we show that eya-1 mutants are highly sensitive to induction of DNA damage, yet show little change to induced DNA replication stress and display a mortal germline resulting in sterility over successive generations.

Collectively, this study suggests that the EYA family of proteins may have a greater involvement in maintaining genomic integrity than previously thought and unveils novel roles of EYA associated DNA damage repair.

The online version contains supplementary material available at 10.1007/s11033-024-09933-4.