Zinc finger transcription factor CASZ1b is involved in the DNA damage response in live cells

Abstract

Zinc finger transcription factor CASZ1b is essential for nervous system development and suppresses neuroblastoma growth. Our previous study showed that CASZ1b interacts with DNA repair proteins, however, whether CASZ1b is involved in the DNA damage response remains unclear. In this study, we investigated the kinetic recruitment of CASZ1b to sites of DNA damage upon induction by laser microirradiation. We find that CASZ1b is transiently recruited to sites of DNA damage in multiple cell lines. Mutagenesis of either the poly-(ADP-ribose) (PAR) binding motif or NuRD complex binding region in CASZ1b significantly reduces the recruitment of CASZ1b to these sites of DNA damage (∼65% and ∼30%, respectively). In addition, treatment of cells with a poly-(ADP-ribose) polymerase (PARP) inhibitor significantly attenuates the recruitment of CASZ1b to these DNA damaged sites. Loss of CASZ1 increases cell sensitivity to DNA damage induced by gamma irradiation as shown by decreased colony formation. Our studies reveal that CASZ1b is transiently recruited to DNA damage sites mainly in a PARP-dependent way and regulates cell sensitivity to DNA damage. Our results suggest that CASZ1b has a role, although perhaps a minor one, in the DNA damage response and ultimately regulating the efficiency of DNA repair during normal development and tumorigenesis.