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

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Item Type:Article
Title:The highly conserved nuclear lamin Ig-fold binds to PCNA: its role in DNA replication
Creators Name: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.
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.
Keywords:Cell Nucleus, Chromatin, DNA Replication, HeLa Cells, Immunoglobulins, Lamin Type A, Lamin Type B, Lamins, Ovum, Proliferating Cell Nuclear Antigen, Protein Binding, Protein Folding, Spermatozoa, Animals, Xenopus laevis
Source:Journal of Cell Biology
ISSN:0021-9525
Publisher:Rockefeller University Press (U.S.A.)
Volume:181
Number:2
Page Range:269-280
Date:21 April 2008
Additional Information:Copyright (c) 2008 by The Rockerfeller University Press
Official Publication:https://doi.org/10.1083/jcb.200708155
PubMed:View item in PubMed

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