Localization-Dependent and -Independent Roles of SLX4 in Regulating Telomeres
SLX4, a scaffold for structure-specific DNA repair nucleases, is important for several types of DNA repair. Many repair proteins bind to sites of DNA damage, resulting in subnuclear “foci,” but SLX4 forms foci in human cells even without DNA damage. Using several approaches, we show that most, but n...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713003951 |
| _version_ | 1818114318932115456 |
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| author | Jamie S.J. Wilson Agueda M. Tejera Dennis Castor Rachel Toth Maria A. Blasco John Rouse |
| author_facet | Jamie S.J. Wilson Agueda M. Tejera Dennis Castor Rachel Toth Maria A. Blasco John Rouse |
| author_sort | Jamie S.J. Wilson |
| collection | DOAJ |
| description | SLX4, a scaffold for structure-specific DNA repair nucleases, is important for several types of DNA repair. Many repair proteins bind to sites of DNA damage, resulting in subnuclear “foci,” but SLX4 forms foci in human cells even without DNA damage. Using several approaches, we show that most, but not all, SLX4 foci localize to telomeres in a range of human cell lines irrespective of the mechanisms used to maintain telomere length. The SLX1 Holliday-junction-processing enzyme is recruited to telomeres by SLX4, and SLX4, in turn, is recruited by a motif that binds to the shelterin subunit TRF2 directly. We also show that TRF2-dependent recruitment of SLX4 prevents telomere damage. Furthermore, SLX4 prevents telomere lengthening and fragility in a manner that appears to be independent of telomere association. These findings reveal that SLX4 plays multiple roles in regulating telomere homeostasis. |
| first_indexed | 2024-12-11T03:48:50Z |
| format | Article |
| id | doaj.art-b95679f503dd4d888e7f8e3f89a2764e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T03:48:50Z |
| publishDate | 2013-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b95679f503dd4d888e7f8e3f89a2764e2022-12-22T01:21:57ZengElsevierCell Reports2211-12472013-09-014585386010.1016/j.celrep.2013.07.033Localization-Dependent and -Independent Roles of SLX4 in Regulating TelomeresJamie S.J. Wilson0Agueda M. Tejera1Dennis Castor2Rachel Toth3Maria A. Blasco4John Rouse5MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UKSpanish National Cancer Research Centre (CNIO), Molecular Oncology Program, Madrid E-28029, SpainMRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UKMRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UKSpanish National Cancer Research Centre (CNIO), Molecular Oncology Program, Madrid E-28029, SpainMRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UKSLX4, a scaffold for structure-specific DNA repair nucleases, is important for several types of DNA repair. Many repair proteins bind to sites of DNA damage, resulting in subnuclear “foci,” but SLX4 forms foci in human cells even without DNA damage. Using several approaches, we show that most, but not all, SLX4 foci localize to telomeres in a range of human cell lines irrespective of the mechanisms used to maintain telomere length. The SLX1 Holliday-junction-processing enzyme is recruited to telomeres by SLX4, and SLX4, in turn, is recruited by a motif that binds to the shelterin subunit TRF2 directly. We also show that TRF2-dependent recruitment of SLX4 prevents telomere damage. Furthermore, SLX4 prevents telomere lengthening and fragility in a manner that appears to be independent of telomere association. These findings reveal that SLX4 plays multiple roles in regulating telomere homeostasis.http://www.sciencedirect.com/science/article/pii/S2211124713003951 |
| spellingShingle | Jamie S.J. Wilson Agueda M. Tejera Dennis Castor Rachel Toth Maria A. Blasco John Rouse Localization-Dependent and -Independent Roles of SLX4 in Regulating Telomeres Cell Reports |
| title | Localization-Dependent and -Independent Roles of SLX4 in Regulating Telomeres |
| title_full | Localization-Dependent and -Independent Roles of SLX4 in Regulating Telomeres |
| title_fullStr | Localization-Dependent and -Independent Roles of SLX4 in Regulating Telomeres |
| title_full_unstemmed | Localization-Dependent and -Independent Roles of SLX4 in Regulating Telomeres |
| title_short | Localization-Dependent and -Independent Roles of SLX4 in Regulating Telomeres |
| title_sort | localization dependent and independent roles of slx4 in regulating telomeres |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713003951 |
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