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The highly conserved nuclear lamin Ig-fold binds to PCNA : its role in DNA replication

Shumaker, D. K. and Solimando, L. and Sengupta, K. and Shimi, T. and Adam, S. A. and Grunwald, A. and Strelkov, S. V. and Aebi, U. and Cardoso, M. C. and Goldman, R. D.. (2008) The highly conserved nuclear lamin Ig-fold binds to PCNA : its role in DNA replication. The Journal of cell biology, Vol. 181, H. 2. pp. 269-280.

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Official URL: http://edoc.unibas.ch/dok/A5259462

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Abstract

This study provides insights into the role of nuclear lamins in DNA replication. Our data demonstrate that the Ig-fold motif located in the lamin C terminus binds directly to proliferating cell nuclear antigen ( PCNA), the processivity factor necessary for the chain elongation phase of DNA replication. We find that the introduction of a mutation in the Ig-fold, which alters its structure and causes human muscular dystrophy, inhibits PCNA binding. Studies of nuclear assembly and DNA replication show that lamins, PCNA, and chromatin are closely associated in situ. Exposure of replicating nuclei to an excess of the lamin domain containing the Ig-fold inhibits DNA replication in a concentration-dependent fashion. This inhibitory effect is significantly diminished in nuclei exposed to the same domain bearing the Ig-fold mutation. Using the crystal structures of the lamin Ig-fold and PCNA, molecular docking simulations suggest probable interaction sites. These findings also provide insights into the mechanisms underlying the numerous disease-causing mutations located within the lamin Ig-fold.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Structural Biology (Aebi)
UniBasel Contributors:Aebi, Ueli
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Rockefeller University Press
ISSN:0021-9525
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:31 Dec 2015 10:42
Deposited On:22 Mar 2012 13:22

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