ATM and ATR Signaling Regulate the Recruitment of Human Telomerase to Telomeres
The yeast homologs of the ATM and ATR DNA damage response kinases play key roles in telomerase-mediated telomere maintenance, but the role of ATM/ATR in the mammalian telomerase pathway has been less clear. Here, we demonstrate the requirement for ATM and ATR in the localization of telomerase to tel...
| Κύριοι συγγραφείς: | , , , , , , |
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| Μορφή: | Άρθρο |
| Γλώσσα: | English |
| Έκδοση: |
Elsevier
2015-11-01
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| Σειρά: | Cell Reports |
| Διαθέσιμο Online: | http://www.sciencedirect.com/science/article/pii/S2211124715012115 |
| _version_ | 1830354364590456832 |
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| author | Adrian S. Tong J. Lewis Stern Agnel Sfeir Melissa Kartawinata Titia de Lange Xu-Dong Zhu Tracy M. Bryan |
| author_facet | Adrian S. Tong J. Lewis Stern Agnel Sfeir Melissa Kartawinata Titia de Lange Xu-Dong Zhu Tracy M. Bryan |
| author_sort | Adrian S. Tong |
| collection | DOAJ |
| description | The yeast homologs of the ATM and ATR DNA damage response kinases play key roles in telomerase-mediated telomere maintenance, but the role of ATM/ATR in the mammalian telomerase pathway has been less clear. Here, we demonstrate the requirement for ATM and ATR in the localization of telomerase to telomeres and telomere elongation in immortal human cells. Stalled replication forks increased telomerase recruitment in an ATR-dependent manner. Furthermore, increased telomerase recruitment was observed upon phosphorylation of the shelterin component TRF1 at an ATM/ATR target site (S367). This phosphorylation leads to loss of TRF1 from telomeres and may therefore increase replication fork stalling. ATM and ATR depletion reduced assembly of the telomerase complex, and ATM was required for telomere elongation in cells expressing POT1ΔOB, an allele of POT1 that disrupts telomere-length homeostasis. These data establish that human telomerase recruitment and telomere elongation are modulated by DNA-damage-transducing kinases. |
| first_indexed | 2024-12-20T01:30:27Z |
| format | Article |
| id | doaj.art-4fd8e00a804548c68ef0c02e8b27f389 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-20T01:30:27Z |
| publishDate | 2015-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-4fd8e00a804548c68ef0c02e8b27f3892022-12-21T19:58:08ZengElsevierCell Reports2211-12472015-11-011381633164610.1016/j.celrep.2015.10.041ATM and ATR Signaling Regulate the Recruitment of Human Telomerase to TelomeresAdrian S. Tong0J. Lewis Stern1Agnel Sfeir2Melissa Kartawinata3Titia de Lange4Xu-Dong Zhu5Tracy M. Bryan6Cell Biology Unit, Children’s Medical Research Institute, University of Sydney, Westmead, NSW 2145, AustraliaCell Biology Unit, Children’s Medical Research Institute, University of Sydney, Westmead, NSW 2145, AustraliaLaboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10065, USACell Biology Unit, Children’s Medical Research Institute, University of Sydney, Westmead, NSW 2145, AustraliaLaboratory for Cell Biology and Genetics, The Rockefeller University, New York, NY 10065, USADepartment of Biology, McMaster University, Hamilton, ON L8S 4K1, CanadaCell Biology Unit, Children’s Medical Research Institute, University of Sydney, Westmead, NSW 2145, AustraliaThe yeast homologs of the ATM and ATR DNA damage response kinases play key roles in telomerase-mediated telomere maintenance, but the role of ATM/ATR in the mammalian telomerase pathway has been less clear. Here, we demonstrate the requirement for ATM and ATR in the localization of telomerase to telomeres and telomere elongation in immortal human cells. Stalled replication forks increased telomerase recruitment in an ATR-dependent manner. Furthermore, increased telomerase recruitment was observed upon phosphorylation of the shelterin component TRF1 at an ATM/ATR target site (S367). This phosphorylation leads to loss of TRF1 from telomeres and may therefore increase replication fork stalling. ATM and ATR depletion reduced assembly of the telomerase complex, and ATM was required for telomere elongation in cells expressing POT1ΔOB, an allele of POT1 that disrupts telomere-length homeostasis. These data establish that human telomerase recruitment and telomere elongation are modulated by DNA-damage-transducing kinases.http://www.sciencedirect.com/science/article/pii/S2211124715012115 |
| spellingShingle | Adrian S. Tong J. Lewis Stern Agnel Sfeir Melissa Kartawinata Titia de Lange Xu-Dong Zhu Tracy M. Bryan ATM and ATR Signaling Regulate the Recruitment of Human Telomerase to Telomeres Cell Reports |
| title | ATM and ATR Signaling Regulate the Recruitment of Human Telomerase to Telomeres |
| title_full | ATM and ATR Signaling Regulate the Recruitment of Human Telomerase to Telomeres |
| title_fullStr | ATM and ATR Signaling Regulate the Recruitment of Human Telomerase to Telomeres |
| title_full_unstemmed | ATM and ATR Signaling Regulate the Recruitment of Human Telomerase to Telomeres |
| title_short | ATM and ATR Signaling Regulate the Recruitment of Human Telomerase to Telomeres |
| title_sort | atm and atr signaling regulate the recruitment of human telomerase to telomeres |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715012115 |
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