Bone morphogenetic protein signaling is required for RAD51-mediated maintenance of genome integrity in vascular endothelial cells.
Yang, Xu Dong
Springer Science and Business Media LLC
MetadataShow full item record
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
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.
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
Medical Research Council (MR/K020919/1)
British Heart Foundation (None)
External DOI: https://doi.org/10.1038/s42003-018-0152-1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286936
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: email@example.com