Exd2-flox Mouse

EXD2, also known as EXDL2, is an exonuclease that plays crucial roles in multiple biological processes. It is involved in DNA double-strand break (DSB) repair, telomere maintenance, replication fork protection, and mitochondrial translation [3,1,2,4]. These functions are essential for genome stability, cell survival, and normal development. Genetic models, such as KO mouse models, are valuable tools to study its functions.

Loss-of-function experiments have revealed significant insights. In ALT-reliant cancers, EXD2 depletion leads to telomere shortening, increased telomeric sister chromatid exchanges, and synthetic lethality when co-depleted with BLM, DNA2 or POLD3, identifying it as a potential druggable target [1]. In cells lacking BRCA1/2, EXD2 deficiency causes fork collapse, hypersensitivity to replication inhibitors, and genomic instability, highlighting its role in protecting stressed replication forks [2]. Additionally, loss of EXD2 in Drosophila results in defective mitochondrial translation, metabolic abnormalities, and lifespan extension [4].

In conclusion, EXD2 is essential for maintaining genome integrity through its functions in DNA repair and replication fork protection. Its role in mitochondrial translation also impacts development and ageing. The findings from KO models in ALT-reliant cancers and cells lacking BRCA1/2 suggest that EXD2 could be a significant target for cancer therapy, further emphasizing the importance of studying EXD2 to understand disease mechanisms and develop treatment strategies.