UV-induced nuclear import of XPA is mediated by importin-α4 in an ATR-dependent manner.
Xeroderma pigmentosum Group A (XPA) is a crucial factor in mammalian nucleotide excision repair (NER) and nuclear import of XPA from the cytoplasm for NER is regulated in cellular DNA damage responses in S-phase. In this study, experiments were carried out to determine the transport mechanisms that...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3704644?pdf=render |
| _version_ | 1818331927530176512 |
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| author | Zhengke Li Phillip R Musich Brian M Cartwright Hui Wang Yue Zou |
| author_facet | Zhengke Li Phillip R Musich Brian M Cartwright Hui Wang Yue Zou |
| author_sort | Zhengke Li |
| collection | DOAJ |
| description | Xeroderma pigmentosum Group A (XPA) is a crucial factor in mammalian nucleotide excision repair (NER) and nuclear import of XPA from the cytoplasm for NER is regulated in cellular DNA damage responses in S-phase. In this study, experiments were carried out to determine the transport mechanisms that are responsible for the UV (ultraviolet)-induced nuclear import of XPA. We found that, in addition to the nuclear localization signal (NLS) of XPA, importin-α4 or/and importin-α7 are required for the XPA nuclear import. Further investigation indicated that, importin-α4 and importin-α7 directly interacted with XPA in cells. Interestingly, the binding of importin-α4 to XPA was dependent on UV-irradiation, while the binding of importin-α7 was not, suggesting a role for importin-α7 in nuclear translocation of XPA in the absence of DNA damage, perhaps with specificity to certain non-S-phases of the cell-cycle. Consistent with the previous report of a dependence of UV-induced XPA nuclear import on ataxia telangiectasia and Rad3-related protein (ATR) in S-phase, knockdown of ATR reduced the amount of XPA interacting with importin-α4. In contrast, the GTPase XPA binding protein 1 (XAB1), previously proposed to be required for XPA nuclear import, showed no effect on the nuclear import of XPA in our siRNA knockdown analysis. In conclusion, our results suggest that upon DNA damage transport adaptor importin-α4 imports XPA into the nucleus in an ATR-dependent manner, while XAB1 has no role in this process. In addition, these findings reveal a potential new therapeutic target for the sensitization of cancer cells to chemotherapy. |
| first_indexed | 2024-12-13T13:27:37Z |
| format | Article |
| id | doaj.art-8113fba0a1c74e31992bbb2cb63e9c2f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T13:27:37Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8113fba0a1c74e31992bbb2cb63e9c2f2022-12-21T23:44:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6829710.1371/journal.pone.0068297UV-induced nuclear import of XPA is mediated by importin-α4 in an ATR-dependent manner.Zhengke LiPhillip R MusichBrian M CartwrightHui WangYue ZouXeroderma pigmentosum Group A (XPA) is a crucial factor in mammalian nucleotide excision repair (NER) and nuclear import of XPA from the cytoplasm for NER is regulated in cellular DNA damage responses in S-phase. In this study, experiments were carried out to determine the transport mechanisms that are responsible for the UV (ultraviolet)-induced nuclear import of XPA. We found that, in addition to the nuclear localization signal (NLS) of XPA, importin-α4 or/and importin-α7 are required for the XPA nuclear import. Further investigation indicated that, importin-α4 and importin-α7 directly interacted with XPA in cells. Interestingly, the binding of importin-α4 to XPA was dependent on UV-irradiation, while the binding of importin-α7 was not, suggesting a role for importin-α7 in nuclear translocation of XPA in the absence of DNA damage, perhaps with specificity to certain non-S-phases of the cell-cycle. Consistent with the previous report of a dependence of UV-induced XPA nuclear import on ataxia telangiectasia and Rad3-related protein (ATR) in S-phase, knockdown of ATR reduced the amount of XPA interacting with importin-α4. In contrast, the GTPase XPA binding protein 1 (XAB1), previously proposed to be required for XPA nuclear import, showed no effect on the nuclear import of XPA in our siRNA knockdown analysis. In conclusion, our results suggest that upon DNA damage transport adaptor importin-α4 imports XPA into the nucleus in an ATR-dependent manner, while XAB1 has no role in this process. In addition, these findings reveal a potential new therapeutic target for the sensitization of cancer cells to chemotherapy.http://europepmc.org/articles/PMC3704644?pdf=render |
| spellingShingle | Zhengke Li Phillip R Musich Brian M Cartwright Hui Wang Yue Zou UV-induced nuclear import of XPA is mediated by importin-α4 in an ATR-dependent manner. PLoS ONE |
| title | UV-induced nuclear import of XPA is mediated by importin-α4 in an ATR-dependent manner. |
| title_full | UV-induced nuclear import of XPA is mediated by importin-α4 in an ATR-dependent manner. |
| title_fullStr | UV-induced nuclear import of XPA is mediated by importin-α4 in an ATR-dependent manner. |
| title_full_unstemmed | UV-induced nuclear import of XPA is mediated by importin-α4 in an ATR-dependent manner. |
| title_short | UV-induced nuclear import of XPA is mediated by importin-α4 in an ATR-dependent manner. |
| title_sort | uv induced nuclear import of xpa is mediated by importin α4 in an atr dependent manner |
| url | http://europepmc.org/articles/PMC3704644?pdf=render |
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