Identification of Regions Required for CDCA7 Interaction with DNA Damage Repair Machinery

CDCA7 (Cell Division Cycle Associated Protein 7) is a transcription factor protein that binds to DNA and histone modifying enzymes supporting DNA methylation and contributes to repair of double stranded breaks in DNA. Mutations of the cdca7 gene cause ICF (Immunodeficiency, centromeric instability, and facial abnormalities) syndrome. CDCA7 has been shown to bind with HELLS (Helicase, lymphoid specific) as a bipartite nucleosome remodeller to allow for de novo methylation by DNMT3b (DNA methyl transferase 3b). Additionally, CDCA7 associates with Ku70 and Ku80, proteins essential for DNA damage repair via the Non-Homologous End Joining (NHEJ) pathway, and -H2AX, whose accumulation is facilitated by Ku proteins and is a biomarker of DNA damage. I show here that CDCA7 requires a putative leucine zipper for association with HELLS, while the binding of 14-3-3 at a phosphorylated residue in CDCA7 regulates Ku70/80 and -H2AX association. This study further elucidates the mechanism of how CDCA7 plays a crucial role in maintaining genomic stability by participating in various DNA repair processes and DNA methylation.