Poly(ADP-Ribose) Links the DNA Damage Response and Biomineralization
Müller, K. H., Hayward, R., Rajan, R. , Whitehead, M., Cobb, A. M. 
ORCID: 0000-0003-2163-5999, Ahmad, S., Sun, M., Goldberga, I., Li, R., Bashtanova, U., Puszkarska, A. M., Reid, D. G., Brooks, R. A., Skepper, J. N., Bordoloi, J., Chow, W. Y., Oschkinat, H., Groombridge, A., Scherman, O. A., Harrison, J. A., Verhulst, A., D’Haese, P. C., Neven, E., Needham, L-M., Lee, S. F., Shanahan, C. M. & Duer, M. J. (2019).
Poly(ADP-Ribose) Links the DNA Damage Response and Biomineralization.
Cell Reports, 27(11),
3124-3138.e13.
doi: 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(ADP-ribose) 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.
| Publication Type: | Article |
|---|---|
| Additional Information: | This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Publisher Keywords: | poly(ADP-ribose), vascular smooth muscle cell, bone, DNA damage |
| Subjects: | Q Science > QH Natural history > QH301 Biology R Medicine > RC Internal medicine |
| Departments: | School of Health & Psychological Sciences |
| SWORD Depositor: |
Available under License Creative Commons Attribution.
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