Bone morphogenetic protein signaling is required for RAD51-mediated maintenance of genome integrity in vascular endothelial cells.
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Authors
Vattulainen-Collanus, Sanna
Southwood, Mark
Yang, Xu Dong
Moore, Stephen
Ghatpande, Prajakta
Lagna, Giorgio
Publication Date
2018Journal Title
Commun Biol
ISSN
2399-3642
Publisher
Springer Science and Business Media LLC
Volume
1
Pages
149
Language
eng
Type
Article
This Version
VoR
Physical Medium
Electronic-eCollection
Metadata
Show full item recordCitation
Vattulainen-Collanus, S., Southwood, M., Yang, X. D., Moore, S., Ghatpande, P., Morrell, N. W., Lagna, G., & et al. (2018). Bone morphogenetic protein signaling is required for RAD51-mediated maintenance of genome integrity in vascular endothelial cells.. Commun Biol, 1 149. https://doi.org/10.1038/s42003-018-0152-1
Abstract
The integrity of blood vessels is fundamental to vascular homeostasis. Inactivating mutations in the bone morphogenetic protein (BMP) receptor type II (BMPR2) gene cause hereditary vascular disorders, including pulmonary arterial hypertension and hereditary hemorrhagic telangiectasia, suggesting that BMPR2 and its downstream signaling pathway are pivotal to the maintenance of vascular integrity through an unknown molecular mechanism. Here we report that inactivation of BMPR2 in pulmonary vascular endothelial cells results in a deficit of RAD51, an enzyme essential for DNA repair and replication. Loss of RAD51, which causes DNA damage and cell death, is also detected in animal models and human patients with pulmonary arterial hypertension. Restoration of BMPR2 or activation of the BMP signaling pathway rescues RAD51 and prevents DNA damage. This is an unexpected role of BMP signaling in preventing the accumulation of DNA damage and the concomitant loss of endothelial integrity and vascular remodeling associated with vascular disorders.
Keywords
0604 Genetics, 0601 Biochemistry and Cell Biology, 1102 Cardiorespiratory Medicine and Haematology, Biomedical, Basic Science, Genetics, Rare Diseases, Cardiovascular, 2.1 Biological and endogenous factors
Sponsorship
Medical Research Council (MR/K020919/1)
British Heart Foundation (None)
Identifiers
External DOI: https://doi.org/10.1038/s42003-018-0152-1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286936
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