DNA damage response during meiosis

Our research interest is the DNA damage response (DDR) during meiosis. We use C. elegans, this nematode is a wonderful model system for meiosis studies and in the last years has proved as a powerful model to understand DDR and genome stability.

Genomic DNA is under constant attack from both endogenous and exogenous DNA damaging agents. Without proper repair the resulting DNA damages would lead to alteration of genomic structure thus affecting the faithful transmission of genetic information. In addition, defects during meiosis lead to aneuploidy, an extreme kind of genetic instability associated with fertility problems, miscarriages and mental retardation syndromes. Very little is known about the relationship between the meiosis progression and the DNA damage response. Since cells undergoing meiosis during oogenesis stay arrested in meiosis I for long periods of time and therefore vulnerable to DNA lesions we speculated if the increase in genome instability inferred from the increase in aneuploidy that correlates with mother age might be related to defects in DDR during meiosis. Phosphorylation is a key regulator in many processes and therefore an obvious first candidate to analyse, and key kinases of DNA damage checkpoints are ATR and ATM. The aim is to address at the molecular level the biological relevance of the DNA damage dependent phosphorylations observed in silico with the peptide array technique and to determine how ATR/ATM DNA damage phosphorylations contribute to the regulation of different DNA repair pathways, both to ensure genome stability of meiotic cells.

   This knowledge of DDR regulation during meiosis should, therefore, provide important insights into fertility defects diagnosis and may present opportunities for therapeutic intervention.

ORCID: 0000-0002-3195-2261

Researcher ID: F-1339-2016

Scopus: 6506810877