Itamar Harel

Congratulations to Itamar Harel, Zuckerman Faculty Scholar in the Department of Genetics at the Hebrew University of Jerusalem, on the publication of his latest study, A dual role for cGAS in shaping cellular and organismal responses to genomic instability, in Genes and Development.

The study tackles the question of cells that cannot properly repair damaged DNA and focuses on cGAS, an internal alarm-like protein that senses DNA in the wrong place that can trigger inflammation. Using genetic models of DNA repair syndromes in the turquoise killifish, Dr. Harel and his team demonstrate that turning off this “alarm” partly reduces major disease signals including infertility, liver aging, and brain inflammation. They also discovered that removing cGAS improves several cellular signs of genome instability, suggesting its influence on DNA repair inside the cell as well.

Abstract:
Mutations in DNA damage repair (DDR) genes lead to genomic instability, driving a range of degenerative syndromes. In addition to promoting mutation accumulation, unrepaired DNA damage can leak into the cytosol and activate innate immune sensing pathways, particularly the cGAS-STING axis… The findings support pharmacological cGAS inhibition as a potential strategy for DDR syndromes in settings of chronic DNA damage while highlighting that cgas loss in an otherwise naive background exacerbates pathology and genomic instability, underscoring its essential role in normal physiology.