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

Nat Commun. 2019 Dec 3;10(1):5501. doi: 10.1038/s41467-019-13167-5.

Emma Bolderson ¹ ², Joshua T Burgess ³, Jun Li ⁴ ⁵, Neha S Gandhi ⁶, Didier Boucher ³, Laura V Croft ³, Samuel Beard ³, Jennifer J Plowman ³, Amila Suraweera ³, Mark N Adams ³, Ali Naqi ³ ⁷, Shu-Dong Zhang ⁸, David A Sinclair ⁴ ⁹, Kenneth J O'Byrne ³ ¹⁰, Derek J Richard ¹¹ ¹²

Affiliations

1 Cancer & Ageing Research Program, Institute of Health and Biomedical Innovation at the Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, Queensland, Australia. emma.bolderson@qut.edu.au.
2 Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Queensland, 4102, Australia. emma.bolderson@qut.edu.au.
3 Cancer & Ageing Research Program, Institute of Health and Biomedical Innovation at the Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, Queensland, Australia.
4 Department of Genetics, Paul F. Glenn Center for Biology of Aging Research, Harvard Medical School, Boston, MA, 02115, USA.
5 National Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China.
6 School of Mathematical Sciences, Queensland University of Technology, Brisbane, 4000, Queensland, Australia.
7 Department of Chemistry, Pennsylvania State University, University Park, PA, USA.
8 Northern Ireland Centre for Stratified Medicine, University of Ulster, Londonderry, UK.
9 The Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, 2052, Australia.
10 Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Queensland, 4102, Australia.
11 Cancer & Ageing Research Program, Institute of Health and Biomedical Innovation at the Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, Queensland, Australia. derek.richard@qut.edu.au.
12 Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Queensland, 4102, Australia. derek.richard@qut.edu.au.

PMID: 31796734 DOI: 10.1038/s41467-019-13167-5

Abstract

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.

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