[PhD Thesis Public Presentation_Zoom] ‐ Swathy Babu– “Banp regulates DNA damage response and chromosome segregation to promote cell-cycle progression and cell survival in zebrafish retina.”

Presenter: Swathy Babu

Supervisor: Prof. Ichiro Masai

Unit: Developmental Neurobiology Unit

Zoom URL: Finished

Title: Banp regulates DNA damage response and chromosome segregation to promote cell-cycle progression and cell survival in zebrafish retina.

Abstract:

Btg3 associated nuclear protein (Banp) was initially identified as a nuclear matrix associated protein and is a tumor suppressor. Recently it was reported that Banp binds to the CGCG sequence enriched near the transcription initiation site of CpG island promoters, namely Banp motif, promotes the transcription in a DNA methylation dependent manner, and controls metabolic genes in pluripotent stem and differentiated neuronal cells. However, cellular roles of Banp in embryonic development remains to be elucidated. Here we report a novel role of Banp in cell-cycle progression and cell survival of zebrafish retinal progenitor cells. In zebrafish banp mutants, retinal progenitor cells showed mitotic arrest and subsequent apoptosis. DNA replication stress and tp53-dependent DNA damage response were activated in banp mutants. Inhibition of tp53 significantly rescued apoptosis but not mitotic arrest and DNA double strand break accumulation, suggesting that Banp is required for functional integrity of DNA replication and DNA damage repair. Furthermore, live imaging of mitosis in banp mutant retinas revealed that chromosome segregation was not smoothly processed from prometaphase to anaphase, leading to prolonged M phase. Bulk RNAseq analysis show that mRNA expression of two chromosomal segregation regulators, cenpt and ncapg, were decreased in banp mutants. Furthermore, ATACseq analysis showed that chromatin near their transcription start site was closed in banp mutants and indeed Banp motif was found in this chromatin-closed region, suggesting that Banp directly regulates cenpt and ncapg transcription to promote chromosome segregation during mitosis. Our findings reveal that Banp is required for cell-cycle progression and cell survival by regulating DNA damage response and chromosome segregation during mitosis