The N Terminus of the OB Domain of Telomere Protein TPP1 Is Critical for Telomerase Action
Summary: Telomerase recruitment to telomeres and enzymatic processivity are mediated by TPP1, an essential component of telomere integrity and telomerase function. A surface on the OB domain of TPP1 called the TEL patch is critical for TPP1’s telomerase-associated functions. Here, we identify a sepa...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-01-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718300299 |
| _version_ | 1818332880250601472 |
|---|---|
| author | Sherilyn Grill Valerie M. Tesmer Jayakrishnan Nandakumar |
| author_facet | Sherilyn Grill Valerie M. Tesmer Jayakrishnan Nandakumar |
| author_sort | Sherilyn Grill |
| collection | DOAJ |
| description | Summary: Telomerase recruitment to telomeres and enzymatic processivity are mediated by TPP1, an essential component of telomere integrity and telomerase function. A surface on the OB domain of TPP1 called the TEL patch is critical for TPP1’s telomerase-associated functions. Here, we identify a separate region in the N terminus of the OB domain (termed NOB) of TPP1 that, like the TEL patch, is essential for telomerase repeat addition processivity in vitro as well as telomerase recruitment to telomeres and telomere lengthening in cells. Although well-conserved among most mammalian TPP1 homologs, the NOB region in mice is distinct. Swapping the sequence of human NOB into mouse TPP1 allows it to stimulate human telomerase, qualifying NOB as an important determinant of species specificity for TPP1-telomerase interaction. Our studies show that TPP1 NOB is critical for telomerase function and demonstrate that the telomerase interaction surface on TPP1 is more elaborate than previously appreciated. : TPP1 protein is critical for telomerase function and telomere length maintenance. Grill et al. find that the TPP1 NOB region is part of the surface that mediates these functions. The inability of mouse TPP1 to stimulate human telomerase is partially rescued by swapping in the human NOB sequence. Keywords: telomerase, telomeres, TPP1, TEL patch, telomerase processivity, telomerase recruitment, shelterin |
| first_indexed | 2024-12-13T13:42:46Z |
| format | Article |
| id | doaj.art-8709c8320b374b5f99cee9b032539a5f |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T13:42:46Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-8709c8320b374b5f99cee9b032539a5f2022-12-21T23:43:32ZengElsevierCell Reports2211-12472018-01-0122511321140The N Terminus of the OB Domain of Telomere Protein TPP1 Is Critical for Telomerase ActionSherilyn Grill0Valerie M. Tesmer1Jayakrishnan Nandakumar2Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USADepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USADepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA; Corresponding authorSummary: Telomerase recruitment to telomeres and enzymatic processivity are mediated by TPP1, an essential component of telomere integrity and telomerase function. A surface on the OB domain of TPP1 called the TEL patch is critical for TPP1’s telomerase-associated functions. Here, we identify a separate region in the N terminus of the OB domain (termed NOB) of TPP1 that, like the TEL patch, is essential for telomerase repeat addition processivity in vitro as well as telomerase recruitment to telomeres and telomere lengthening in cells. Although well-conserved among most mammalian TPP1 homologs, the NOB region in mice is distinct. Swapping the sequence of human NOB into mouse TPP1 allows it to stimulate human telomerase, qualifying NOB as an important determinant of species specificity for TPP1-telomerase interaction. Our studies show that TPP1 NOB is critical for telomerase function and demonstrate that the telomerase interaction surface on TPP1 is more elaborate than previously appreciated. : TPP1 protein is critical for telomerase function and telomere length maintenance. Grill et al. find that the TPP1 NOB region is part of the surface that mediates these functions. The inability of mouse TPP1 to stimulate human telomerase is partially rescued by swapping in the human NOB sequence. Keywords: telomerase, telomeres, TPP1, TEL patch, telomerase processivity, telomerase recruitment, shelterinhttp://www.sciencedirect.com/science/article/pii/S2211124718300299 |
| spellingShingle | Sherilyn Grill Valerie M. Tesmer Jayakrishnan Nandakumar The N Terminus of the OB Domain of Telomere Protein TPP1 Is Critical for Telomerase Action Cell Reports |
| title | The N Terminus of the OB Domain of Telomere Protein TPP1 Is Critical for Telomerase Action |
| title_full | The N Terminus of the OB Domain of Telomere Protein TPP1 Is Critical for Telomerase Action |
| title_fullStr | The N Terminus of the OB Domain of Telomere Protein TPP1 Is Critical for Telomerase Action |
| title_full_unstemmed | The N Terminus of the OB Domain of Telomere Protein TPP1 Is Critical for Telomerase Action |
| title_short | The N Terminus of the OB Domain of Telomere Protein TPP1 Is Critical for Telomerase Action |
| title_sort | n terminus of the ob domain of telomere protein tpp1 is critical for telomerase action |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718300299 |
| work_keys_str_mv | AT sherilyngrill thenterminusoftheobdomainoftelomereproteintpp1iscriticalfortelomeraseaction AT valeriemtesmer thenterminusoftheobdomainoftelomereproteintpp1iscriticalfortelomeraseaction AT jayakrishnannandakumar thenterminusoftheobdomainoftelomereproteintpp1iscriticalfortelomeraseaction AT sherilyngrill nterminusoftheobdomainoftelomereproteintpp1iscriticalfortelomeraseaction AT valeriemtesmer nterminusoftheobdomainoftelomereproteintpp1iscriticalfortelomeraseaction AT jayakrishnannandakumar nterminusoftheobdomainoftelomereproteintpp1iscriticalfortelomeraseaction |