SLX4 Assembles a Telomere Maintenance Toolkit by Bridging Multiple Endonucleases with Telomeres
SLX4 interacts with several endonucleases to resolve structural barriers in DNA metabolism. SLX4 also interacts with telomeric protein TRF2 in human cells. The molecular mechanism of these interactions at telomeres remains unknown. Here, we report the crystal structure of the TRF2-binding motif of S...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2013-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124713004580 |
| _version_ | 1818066077879369728 |
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| author | Bingbing Wan Jinhu Yin Kent Horvath Jaya Sarkar Yong Chen Jian Wu Ke Wan Jian Lu Peili Gu Eun Young Yu Neal F. Lue Sandy Chang Yie Liu Ming Lei |
| author_facet | Bingbing Wan Jinhu Yin Kent Horvath Jaya Sarkar Yong Chen Jian Wu Ke Wan Jian Lu Peili Gu Eun Young Yu Neal F. Lue Sandy Chang Yie Liu Ming Lei |
| author_sort | Bingbing Wan |
| collection | DOAJ |
| description | SLX4 interacts with several endonucleases to resolve structural barriers in DNA metabolism. SLX4 also interacts with telomeric protein TRF2 in human cells. The molecular mechanism of these interactions at telomeres remains unknown. Here, we report the crystal structure of the TRF2-binding motif of SLX4 (SLX4TBM) in complex with the TRFH domain of TRF2 (TRF2TRFH) and map the interactions of SLX4 with endonucleases SLX1, XPF, and MUS81. TRF2 recognizes a unique HxLxP motif on SLX4 via the peptide-binding site in its TRFH domain. Telomeric localization of SLX4 and associated nucleases depend on the SLX4-endonuclease and SLX4-TRF2 interactions and the protein levels of SLX4 and TRF2. SLX4 assembles an endonuclease toolkit that negatively regulates telomere length via SLX1-catalyzed nucleolytic resolution of telomere DNA structures. We propose that the SLX4-TRF2 complex serves as a double-layer scaffold bridging multiple endonucleases with telomeres for recombination-based telomere maintenance. |
| first_indexed | 2024-12-10T15:02:03Z |
| format | Article |
| id | doaj.art-a044fd0be695404b8c7edd6a050e629a |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T15:02:03Z |
| publishDate | 2013-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-a044fd0be695404b8c7edd6a050e629a2022-12-22T01:44:08ZengElsevierCell Reports2211-12472013-09-014586186910.1016/j.celrep.2013.08.017SLX4 Assembles a Telomere Maintenance Toolkit by Bridging Multiple Endonucleases with TelomeresBingbing Wan0Jinhu Yin1Kent Horvath2Jaya Sarkar3Yong Chen4Jian Wu5Ke Wan6Jian Lu7Peili Gu8Eun Young Yu9Neal F. Lue10Sandy Chang11Yie Liu12Ming Lei13State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, ChinaLaboratory of Molecular Gerontology, National Institute on Aging/National Institute of Health, 251 Bayview Drive, Baltimore, MD 21044, USALaboratory of Molecular Gerontology, National Institute on Aging/National Institute of Health, 251 Bayview Drive, Baltimore, MD 21044, USALaboratory of Molecular Gerontology, National Institute on Aging/National Institute of Health, 251 Bayview Drive, Baltimore, MD 21044, USAState Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, ChinaState Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, ChinaHoward Hughes Medical Institute, University of Michigan Medical School, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USALaboratory of Molecular Gerontology, National Institute on Aging/National Institute of Health, 251 Bayview Drive, Baltimore, MD 21044, USADepartment of Laboratory Medicine and Pathology, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520, USADepartment of Microbiology and Immunology, W. R. Hearst Microbiology Research Center, Weill Medical College of Cornell University, New York, NY 10065, USADepartment of Microbiology and Immunology, W. R. Hearst Microbiology Research Center, Weill Medical College of Cornell University, New York, NY 10065, USADepartment of Laboratory Medicine and Pathology, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520, USALaboratory of Molecular Gerontology, National Institute on Aging/National Institute of Health, 251 Bayview Drive, Baltimore, MD 21044, USAState Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, ChinaSLX4 interacts with several endonucleases to resolve structural barriers in DNA metabolism. SLX4 also interacts with telomeric protein TRF2 in human cells. The molecular mechanism of these interactions at telomeres remains unknown. Here, we report the crystal structure of the TRF2-binding motif of SLX4 (SLX4TBM) in complex with the TRFH domain of TRF2 (TRF2TRFH) and map the interactions of SLX4 with endonucleases SLX1, XPF, and MUS81. TRF2 recognizes a unique HxLxP motif on SLX4 via the peptide-binding site in its TRFH domain. Telomeric localization of SLX4 and associated nucleases depend on the SLX4-endonuclease and SLX4-TRF2 interactions and the protein levels of SLX4 and TRF2. SLX4 assembles an endonuclease toolkit that negatively regulates telomere length via SLX1-catalyzed nucleolytic resolution of telomere DNA structures. We propose that the SLX4-TRF2 complex serves as a double-layer scaffold bridging multiple endonucleases with telomeres for recombination-based telomere maintenance.http://www.sciencedirect.com/science/article/pii/S2211124713004580 |
| spellingShingle | Bingbing Wan Jinhu Yin Kent Horvath Jaya Sarkar Yong Chen Jian Wu Ke Wan Jian Lu Peili Gu Eun Young Yu Neal F. Lue Sandy Chang Yie Liu Ming Lei SLX4 Assembles a Telomere Maintenance Toolkit by Bridging Multiple Endonucleases with Telomeres Cell Reports |
| title | SLX4 Assembles a Telomere Maintenance Toolkit by Bridging Multiple Endonucleases with Telomeres |
| title_full | SLX4 Assembles a Telomere Maintenance Toolkit by Bridging Multiple Endonucleases with Telomeres |
| title_fullStr | SLX4 Assembles a Telomere Maintenance Toolkit by Bridging Multiple Endonucleases with Telomeres |
| title_full_unstemmed | SLX4 Assembles a Telomere Maintenance Toolkit by Bridging Multiple Endonucleases with Telomeres |
| title_short | SLX4 Assembles a Telomere Maintenance Toolkit by Bridging Multiple Endonucleases with Telomeres |
| title_sort | slx4 assembles a telomere maintenance toolkit by bridging multiple endonucleases with telomeres |
| url | http://www.sciencedirect.com/science/article/pii/S2211124713004580 |
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