‘Regulation of PARP1 activity and DNA repair capacity by the c-Abl kinase Banf1 nexus’

Host: Tom Owen Hughes

Venue: Sir Kenneth & Lady Noreen Murray Seminar Room, CTIR 2.84

Abstract:

Maintaining genome integrity requires precise regulation of DNA repair enzymes, yet how these activities are switched on and off remains incompletely understood. In this seminar, I will present our discovery of a novel regulatory axis connecting the tyrosine kinase c-Abl, the nuclear envelope protein BANF1, and the DNA repair enzyme PARP1. We find that c-Abl phosphorylates both BANF1 and PARP1, enabling BANF1 to move from a dimer to a monomer, where it binds directly to NAD+ binding pocket of PARP1. Strikingly, BANF1 binding, within the NAD⁺ binding pocket of PARP1, also requires c-Abl phosphorylation of PARP1 at Y907.  BanF1 functions as a steric inhibitor, sitting over the NAD+ binding pocket of PARP1, preventing catalytic activity and thereby blocking DNA repair. This c-Abl–BANF1–PARP1 nexus represents a new mechanism by which kinase signaling controls DNA repair capacity, with this nexus having specific implications in the natural ageing process and disease.

Bio: 

Derek Richard was educated in Dundee! He went to school at Menzieshill High School, then studied at Dundee University as an undergraduate and PhD student. He finished his PhD supervised by David Boxer in 199.  He then worked as a postdoctoral fellow with Stefan Roberts in Gene Regulation before moving to St Andrews to study Archaea DNA repair proteins with Malcolm White.  He moved to Queensland in 2004 to join the team of Prof Kum Kum Khanna at QIMR and was the first to characterise the human SSB family of proteins, then moved his research team to the Institute of Health and Biomedical Innovation at QUT in Feb 2011. He is currently Scientific Director of the Cancer and Ageing Research Program and Director of the Queensland Centre for Drug Target Screening.  His research group have made important contributions to the understanding of genome stability, resulting in clinical trials and the establishment of spin out companies.