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

By Dale K. Shumaker, Liliana Solimando, Kaushik Sengupta, Takeshi Shimi, Stephen A. Adam, Antje Grunwald, Sergei V. Strelkov, Ueli Aebi, M. Cristina Cardoso and Robert D. Goldman


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

Topics: Research Articles
Publisher: The Rockefeller University Press
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Provided by: PubMed Central
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    1. (2001). A role for nuclear lamins in nuclear envelope assembly.
    2. (2004). A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation.
    3. (2004). Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome.
    4. (1985). Changes in the nuclear distribution of cyclin (PCNA) but not its synthesis depend on DNA replication.
    5. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    6. (2004). ClusPro: an automated docking and discrimination method for the prediction of protein complexes.
    7. (1989). Disassembly of the nuclear envelope of spisula oocytes in a cell-free system.
    8. (2000). Dynamics of DNA replication factories in living cells.
    9. (1991). Expression of chicken lamin B2 in Escherichia coli : characterization of its structure, assembly, and molecular interactions.
    10. (1986). Initiation of DNA replication in nuclei and purifi ed DNA by a cell-free extract of Xenopus eggs.
    11. (1995). Lagging strand DNA synthesis at the eukaryotic replication fork involves binding and stimulation of FEN-1 by proliferating cell nuclear antigen.
    12. (2000). Lamina-associated polypeptide 2alpha binds intranuclear A-type lamins.
    13. (1990). Mechanism of elongation of primed DNA by DNA polymerase delta, proliferating cell nuclear antigen, and activator 1.
    14. (1999). Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.
    15. (2002). Nuclear lamins: building blocks of nuclear architecture.
    16. (2000). Nuclear organization of DNA replication in primary mammalian cells.
    17. (1993). Nuclei that lack a lamina accumulate karyophilic proteins and assemble a nuclear matrix.
    18. (2005). Out-of-plane motions in open sliding clamps: molecular dynamics simulations of eukaryotic and archaeal proliferating cell nuclear antigen.
    19. (2004). Structural analysis of a eukaryotic sliding DNA clamp-clamp loader complex.
    20. (2002). Structure of the globular tail of nuclear lamin.
    21. (1997). SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling.
    22. (2005). The nuclear lamina comes of age.
    23. (1986). The nuclear lamina is a meshwork of intermediate-type fi laments.
    24. (1992). Three-dimensional structure of the beta subunit of E. coli DNA polymerase III holoenzyme: a sliding DNA clamp.
    25. (1995). Xenopus lamin B3 has a direct role in the assembly of a replication competent nucleus: evidence from cell-free egg extracts.

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