Research Projects

Chromatin-dependent DNA Damage Response pathways are crucial for organisms' genomic integrity. TONSOKU, or TONSL, binds the epigenetic mark H4K20me0 on newly synthesized histones during DNA replication and marks post-replicative chromatin until G2/M. It and its partner MMS22L promote homologous recombination to prevent double strand breaks during S-phase. Mutations in the TONSL gene have been linked to SPONASTRIME Dysplasia, a rare autosomal-recessive skeletal dysplasia. This study aims to characterize TONSL UBL and TONSL LRR domains, containing key mutations in SPONASTRIME Dysplasia, both structurally and functionally. The aim is to understand the molecular mechanism of these mutations and the structure-function correlation between TONSL mutations and SPONASTRIME Dysplasia through biophysical, biochemical, and molecular biology experiments.