Journal Article

Barrier-to-autointegration factor 1 (Banf1) regulates poly ADP-ribose polymerase 1 (PARP1) activity following oxidative DNA damage

Boucher, Didier, Sinclair, David A., O’Byrne, Kenneth J., Zhang, Shu-Dong, Adams, Mark N., Suraweera, Amila, Naqi, Ali, Bolderson, Emma, Burgess, Joshua T., Gandhi, Neha S., Croft, Laura V., Li, Jun, Plowman, Jennifer J., Richard, Derek J., Beard, Samuel

2019

Overview

The DNA repair capacity of human cells declines with age, in a process that is not clearly understood. Mutation of the nuclear envelope protein barrier-to-autointegration factor 1 (Banf1) has previously been shown to cause a human progeroid disorder, Néstor–Guillermo progeria syndrome (NGPS). The underlying links between Banf1, DNA repair and the ageing process are unknown. Here, we report that Banf1 controls the DNA damage response to oxidative stress via regulation of poly [ADP-ribose] polymerase 1 (PARP1). Specifically, oxidative lesions promote direct binding of Banf1 to PARP1, a critical NAD + -dependent DNA repair protein, leading to inhibition of PARP1 auto-ADP-ribosylation and defective repair of oxidative lesions, in cells with increased Banf1. Consistent with this, cells from patients with NGPS have defective PARP1 activity and impaired repair of oxidative lesions. These data support a model whereby Banf1 is crucial to reset oxidative-stress-induced PARP1 activity. Together, these data offer insight into Banf1-regulated, PARP1-directed repair of oxidative lesions. Mutation of the nuclear envelope protein, barrier-to-autointegration factor 1 (Banf1), has previously been associated with the development of ageing associated diseases in a human progeria syndrome. Here, the authors reveal the functional link between Banf1-regulated, PARP1-directed repair of oxidative lesions.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14 / 14/1 / 14/63 / 631/337/1427/2123 / 631/80 / 96/1 / Adenosine diphosphate / ADP-ribosylation / Aging / Cell Line, Tumor / Damage / Deoxyribonucleic acid / DNA / DNA Damage / DNA repair / DNA-Binding Proteins - genetics / DNA-Binding Proteins - metabolism / HEK293 Cells / Humanities and Social Sciences / Humans / Lesions / multidisciplinary / Mutation / Mutation - genetics / NAD / Oxidation / Oxidative Stress / Poly (ADP-Ribose) Polymerase-1 - chemistry / Poly (ADP-Ribose) Polymerase-1 - metabolism / Poly Adenosine Diphosphate Ribose - metabolism / Poly(ADP-ribose) polymerase / Progeria / Progeria - metabolism / Protein Binding / Protein Domains / Proteins / Repair / Ribose / Ribosylation / Science / Science (multidisciplinary) / Viral envelope proteins