Poly(ADP-Ribose) Links the DNA Damage Response and Biomineralization
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Authors
Hayward, Robert
Rajan, Rakesh
Whitehead, Meredith
Cobb, Andrew M
Ahmad, Sadia
Sun, Mengxi
Goldberga, Ieva
Li, Rui
Bashtanova, Uliana
Puszkarska, Anna M
Brooks, Roger
Skepper, Jeremy N
Bordoloi, Jayanta
Chow, Wing Ying
Oschkinat, Hartmut
Groombridge, Alex
Harrison, James A
Verhulst, Anja
D'Haese, Patrick C
Needham, Lisa-Maria
Lee, Steven F
Shanahan, Catherine M
Duer, Melinda J
Journal Title
Cell Reports
ISSN
2211-1247
Publisher
Elsevier
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Mueller, K., Hayward, R., Rajan, R., Whitehead, M., Cobb, A. M., Ahmad, S., Sun, M., et al. Poly(ADP-Ribose) Links the DNA Damage Response and Biomineralization. Cell Reports https://doi.org/10.1016/j.celrep.2019.05.038
Abstract
Biomineralization of the extracellular matrix is an essential, regulated process. Inappropriate mineralization of bone and the vasculature has devastating effects on patient health, yet an integrated understanding
of the chemical and cell biological processes that lead to mineral nucleation remains elusive. Here, we report that biomineralization of
bone and the vasculature is associated with extracellular
poly(ADP-ribose) synthesized by poly(ADPribose) polymerases in response to oxidative and/or DNA damage. We use ultrastructural methods to show poly(ADP-ribose) can form both calcified
spherical particles, reminiscent of those found in vascular calcification, and biomimetically calcified collagen fibrils similar to bone. Importantly, inhibition of poly(ADP-ribose) biosynthesis in vitro and in vivo
inhibits biomineralization, suggesting a therapeutic route for the treatment of vascular calcifications. We conclude that poly(ADP-ribose) plays a central chemical role in both pathological and physiological extracellular matrix calcification.
Sponsorship
British Heart Foundation (PG/10/43/28390)
MRC (MR/J007692/1)
MRC (MR/M01066X/1)
Identifiers
External DOI: https://doi.org/10.1016/j.celrep.2019.05.038
This record's URL: https://www.repository.cam.ac.uk/handle/1810/311690