The cell cycle revisited: DNA replication past S phase preserves genome integrity

Bournaka, Spyridoula; Badra-Fajardo, Nibal; Arbi, Marina; Taraviras, Stavros; Lygerou, Zoi

doi:10.1016/j.semcancer.2024.02.002

Seminars in Cancer Biology

2024

DOI: 10.1016/j.semcancer.2024.02.002

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The cell cycle revisited: DNA replication past S phase preserves genome integrity

Spyridoula Bournaka,

Nibal Badra-Fajardo,

Marina Arbi

et al.

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2024

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

Tatnell,

Novakovic,

Boag

et al. 2024

Preprint

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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 single and double stranded DNA breaks are resolved which prevents potential 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 dsDNA break repair. Current understanding of mammalian EYA associated dsDNA break repair is that EYA1 is recruited in response to H2AX signalling. 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 contributed to dsDNA break repair independent of H2AX. At a protein level, the active site of C. elegans EYA-1 is conserved in humans and homology modelling shows structural similarity to human EYA1. Absence of eya-1 results in abnormal chromosome morphology in anaphase embryos, including chromosomal bridges, missegregated chromosomes, and embryos with abnormal nuclei. eya-1 mutants are highly sensitive to induction of dsDNA breaks yet show little change to ssDNA break inducement. Additionally, eya-1 mutants display a mortal germline phenotype suggesting a generational inheritance of accumulative mutations. 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.

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

Tatnell,

Novakovic,

Boag

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

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The cell cycle revisited: DNA replication past S phase preserves genome integrity

Cited by 1 publication

References 153 publications

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

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

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