Nuclear translocation contributes to regulation of DNA excision repair activities
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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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]”
From UV-Induced Nuclear Import of XPA Is Mediated by Importin-α4 in An ATR-Dependent Manner (2013) · cites this paper as [31]
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].”
From UV-Induced Nuclear Import of XPA Is Mediated by Importin-α4 in An ATR-Dependent Manner (2013) · cites this paper as [31]
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].”
From UV-Induced Nuclear Import of XPA Is Mediated by Importin-α4 in An ATR-Dependent Manner (2013) · cites this paper as [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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