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Apollo, an Artemis-related nuclease, interacts with TRF2 and protects human telomeres in S phase.
- Source :
-
Current biology : CB [Curr Biol] 2006 Jul 11; Vol. 16 (13), pp. 1295-302. Date of Electronic Publication: 2006 May 25. - Publication Year :
- 2006
-
Abstract
- Human chromosome ends are protected by shelterin, an abundant six-subunit protein complex that binds specifically to the telomeric-repeat sequences, regulates telomere length, and ensures that chromosome ends do not elicit a DNA-damage response (reviewed in). Using mass spectrometry of proteins associated with the shelterin component Rap1, we identified an SMN1/PSO2 nuclease family member that is closely related to Artemis. We refer to this protein as Apollo and report that Apollo has the ability to localize to telomeres through an interaction with the shelterin component TRF2. Although its low abundance at telomeres indicates that Apollo is not a core component of shelterin, Apollo knockdown with RNAi resulted in senescence and the activation of a DNA-damage signal at telomeres as evidenced by telomere-dysfunction-induced foci (TIFs). The TIFs occurred primarily in S phase, suggesting that Apollo contributes to a processing step associated with the replication of chromosome ends. Furthermore, some of the metaphase chromosomes showed two telomeric signals at single-chromatid ends, suggesting an aberrant telomere structure. We propose that the Artemis-like nuclease Apollo is a shelterin accessory factor required for the protection of telomeres during or after their replication.
- Subjects :
- Cell Line
Chromosomes, Human metabolism
Chromosomes, Human ultrastructure
DNA Damage
DNA Repair Enzymes
Exodeoxyribonucleases analysis
Exodeoxyribonucleases genetics
Humans
Mass Spectrometry
Nuclear Proteins analysis
Nuclear Proteins genetics
RNA Interference
Shelterin Complex
Telomere ultrastructure
Telomere-Binding Proteins metabolism
Deoxyribonucleases metabolism
Exodeoxyribonucleases metabolism
Nuclear Proteins metabolism
S Phase physiology
Telomere metabolism
Telomeric Repeat Binding Protein 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0960-9822
- Volume :
- 16
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Current biology : CB
- Publication Type :
- Academic Journal
- Accession number :
- 16730176
- Full Text :
- https://doi.org/10.1016/j.cub.2006.05.022