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.

Details

Title
Barrier-to-autointegration factor 1 (Banf1) regulates poly [ADP-ribose] polymerase 1 (PARP1) activity following oxidative DNA damage
Author
Bolderson, Emma 1   VIAFID ORCID Logo  ; Burgess, Joshua T 2 ; Li, Jun 3 ; Gandhi, Neha S 4   VIAFID ORCID Logo  ; Boucher, Didier 2 ; Croft, Laura V 2 ; Beard, Samuel 2 ; Plowman, Jennifer J 2 ; Suraweera, Amila 2   VIAFID ORCID Logo  ; Adams, Mark N 2   VIAFID ORCID Logo  ; Naqi, Ali 5 ; Shu-Dong, Zhang 6   VIAFID ORCID Logo  ; Sinclair, David A 7 ; Kenneth J O’Byrne 1 ; Richard, Derek J 1 

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; Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Queensland, Australia 
2  Cancer & Ageing Research Program, Institute of Health and Biomedical Innovation at the Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, Queensland, Australia 
3  Department of Genetics, Paul F. Glenn Center for Biology of Aging Research, Harvard Medical School, Boston, MA, USA; 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, China 
4  School of Mathematical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia 
5  Cancer & Ageing Research Program, Institute of Health and Biomedical Innovation at the Translational Research Institute (TRI), Queensland University of Technology (QUT), Brisbane, Queensland, Australia; Department of Chemistry, Pennsylvania State University, University Park, PA, USA 
6  Northern Ireland Centre for Stratified Medicine, University of Ulster, Londonderry, UK 
7  Department of Genetics, Paul F. Glenn Center for Biology of Aging Research, Harvard Medical School, Boston, MA, USA; The Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia 
Pages
1-12
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-13167-5
ProQuest document ID
2320978642
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.