CITK modulates BRCA1 recruitment at DNA double strand breaks sites through HDAC6.

ABSTRACT: Citron Kinase (CITK) is a protein encoded by the CIT gene, whose pathogenic variants underlie microcephalic phenotypes that characterize MCPH17 syndrome. In neural progenitors, CITK loss leads to microtubule instability, resulting in mitotic spindle positioning defects, cytokinesis failure, and accumulation of DNA double strand breaks (DSBs), ultimately resulting in TP53-dependent senescence and apoptosis. Although DNA damage accumulation has been associated with impaired homologous recombination (HR), the role of CITK in this process and whether microtubule dynamics are involved is still unknown. In this report we show that CITK is required for proper BRCA1 localization at sites of DNA DSBs. We found that CITK's scaffolding, rather than its catalytic activity, is necessary for maintaining

SUBMITTER: Iegiani G 

PROVIDER: S-EPMC12009987 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature