Zinc Finger Protein 350 (ZNF350)

ZBRK1 binds to a specific sequence, GGGxxxCAGxxxTTT, within GADD45 intron 3 that supports the assembly of a nuclear complex minimally containing both ZBRK1 and BRCA1. Through this recognition sequence, ZBRK1 represses transcription in a BRCA1-dependent manner. The results revealed a novel corepressor function for BRCA1 and provided a mechanistic basis for the biologic activity of BRCA1 through sequence-specific transcriptional regulation.ZBRK1 is rapidly degraded upon treatment of an osteosarcoma cell line with the DNA-damaging agents, ultraviolet light and methyl methanesulfonate. Inhibitors of the ubiquitin-proteasome pathway blocked degradation of ZBRK1. Cells expressing this mutant were hypersensitive to DNA damage and were compromised for GADD45 derepression.