Cited by 56DNA Repair MechanismsNuclear Structure and FunctionBacterial Genetics and Biotechnology

Nuclear translocation contributes to regulation of DNA excision repair activities

Knudsen, Nina Østergaard, Andersen, Sofie Dabros, Lützen, Anne, Nielsen, Finn Cilius, Rasmussen, Lene Juel·2009·DNA Repair

Abstract

DNA mutations are circumvented by dedicated specialized excision repair systems, such as the base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR) pathways. Although the individual repair pathways have distinct roles in suppressing changes in the nuclear DNA, it is evident that proteins from the different DNA repair pathways interact [Y. Wang, D. Cortez, P. Yazdi, N. Neff, S.J. Elledge, J. Qin, BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures, Genes Dev. 14 (2000) 927-939; M. Christmann, M.T. Tomicic, W.P. Roos, B. Kaina, Mechanisms of human DNA repair: an update, Toxicology 193 (2003) 3-34; N.B. Larsen, M. Rasmussen, L.J. Rasmussen, Nuclear and mitochondrial DNA repair: similar pathways? Mitochondrion 5 (2005) 89-108]. Protein interactions are not only important for function, but also for regulation of nuclear import that is necessary for proper localization of the repair proteins. This review summarizes the current knowledge on nuclear import mechanisms of DNA excision repair proteins and provides a model that categorizes the import by different mechanisms, including classical nuclear import, co-import of proteins, and alternative transport pathways. Most excision repair proteins appear to contain classical NLS sequences directing their nuclear import, however, additional import mechanisms add alternative regulatory levels to protein import, indirectly affecting protein function. Protein co-import appears to be a mechanism employed by the composite repair systems NER and MMR to enhance and regulate nuclear accumulation of repair proteins thereby ensuring faithful DNA repair.

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Crossref · 10.1016/j.dnarep.2009.03.005

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  • Cargo protein with a classic NLS requires a direct interaction with importin-α to be transported through the nuclear pore complex.

    “Cargo protein with a classic NLS requires a direct interaction with importin-α to be transported through the nuclear pore complex [31], [40], [45], [46], [47]”
  • In unstressed cells, XPA is primarily restricted to the cytoplasm in G1 and S phases, but is present predominantly in the nucleus during G2 phase.

    “However, more recent biochemical fractionation and immunofluorescence studies demonstrate that in unstressed cells XPA is primarily restricted to the cytoplasm of cells in G1 and S phases, though it is present predominately in the nucleus during the G2 phase [24], [25], [31], [32].”
  • The nuclear import of XPA depends on its NLS in cells, which excludes the possibility that XPA is co-imported with other proteins containing a NLS or imported by alternative import mechanisms.

    “The observation that the nuclear import of XPA depended on its NLS in cells excludes the possibility that XPA was co-imported with other proteins containing a NLS, or imported by “alternative import mechanisms” [31].”

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Authors
Knudsen, N. Ø., Andersen, S. D., Lützen, A., Nielsen, F. C., & Rasmussen, L. J.
Affiliations
  • Roskilde University (DK)
  • Copenhagen University Hospital (DK)
Corresponding author
Rasmussen, Lene Juel
Venue
DNA Repair
Publisher
Elsevier BV
Published
2009-06
Volume
8
Issue
6
Pages
682-689
ISSN
  • 1568-7856 (ISSN-L)
  • 1568-7864
OpenAlex
W2014894966
Cited by
56
References
110
Citations by year
2026: 2 · 2025: 4 · 2024: 1 · 2023: 5 · 2022: 1 · 2021: 1 · 2020: 2 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 3 · 2013: 5 · 2012: 12
FWCI
0.64
Type
journal article
Language
en
Open access
closed
Locations
  • DNA repair (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
  • RUCforsk (Roskilde University) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
nuclear import, excision repair, nucleotide excision repair, DNA mismatch repair, base excision repair, nuclear localization signal, protein-protein interaction
MeSH terms
Cell Nucleus, DNA, DNA Repair, Humans, Protein Transport, Active Transport, Cell Nucleus

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