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TRF2 and Apollo Cooperate with Topoisomerase 2α to Protect Human Telomeres from Replicative Damage
- Source :
- Cell, Cell, 2010, 142 (2), pp.230-242. ⟨10.1016/j.cell.2010.05.032⟩, Cell, Elsevier, 2010, 142 (2), pp.230-242. ⟨10.1016/j.cell.2010.05.032⟩, Cell, Elsevier, 2010, 142 (2), pp.230-42. ⟨10.1016/j.cell.2010.05.032⟩
- Publication Year :
- 2010
- Publisher :
- Elsevier BV, 2010.
-
Abstract
- International audience; Human telomeres are protected from DNA damage by a nucleoprotein complex that includes the repeat-binding factor TRF2. Here, we report that TRF2 regulates the 5' exonuclease activity of its binding partner, Apollo, a member of the metallo-beta-lactamase family that is required for telomere integrity during S phase. TRF2 and Apollo also suppress damage to engineered interstitial telomere repeat tracts that were inserted far away from chromosome ends. Genetic data indicate that DNA topoisomerase 2alpha acts in the same pathway of telomere protection as TRF2 and Apollo. Moreover, TRF2, which binds preferentially to positively supercoiled DNA substrates, together with Apollo, negatively regulates the amount of TOP1, TOP2alpha, and TOP2beta at telomeres. Our data are consistent with a model in which TRF2 and Apollo relieve topological stress during telomere replication. Our work also suggests that cellular senescence may be caused by topological problems that occur during the replication of the inner portion of telomeres.
- Subjects :
- [SDV]Life Sciences [q-bio]
MESH: Antigens, Neoplasm
MESH: DNA Replication
chemistry.chemical_compound
MESH: Protein Structure, Tertiary
0302 clinical medicine
Telomeric Repeat Binding Protein 2
ComputingMilieux_MISCELLANEOUS
Cellular Senescence
Genetics
Telomere-binding protein
0303 health sciences
Nuclear Proteins
MESH: Telomeric Repeat Binding Protein 2
Telomere
DNA-Binding Proteins
MESH: DNA Repair Enzymes
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
MESH: Cell Aging
030220 oncology & carcinogenesis
DNA supercoil
Cell aging
DNA Replication
DNA damage
DNA repair
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Antigens, Neoplasm
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
030304 developmental biology
MESH: DNA Topoisomerases, Type II, Eukaryotic
MESH: DNA Damage
MESH: Humans
Biochemistry, Genetics and Molecular Biology(all)
DNA replication
DNA
Protein Structure, Tertiary
DNA Repair Enzymes
DNA Topoisomerases, Type II
Exodeoxyribonucleases
chemistry
MESH: Telomere
MESH: Nuclear Proteins
MESH: DNA-Binding Proteins
DNA Damage
Subjects
Details
- ISSN :
- 00928674 and 10974172
- Volume :
- 142
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Cell
- Accession number :
- edsair.doi.dedup.....c7b3259112ac3c7f0b1fb27e495f2a67
- Full Text :
- https://doi.org/10.1016/j.cell.2010.05.032