PMID- 20404094
OWN - NLM
STAT- MEDLINE
DCOM- 20100617
LR  - 20221011
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 30
IP  - 12
DP  - 2010 Jun
TI  - TIN2-tethered TPP1 recruits human telomerase to telomeres in vivo.
PG  - 2971-82
LID - 10.1128/MCB.00240-10 [doi]
AB  - Recruitment to telomeres is a pivotal step in the function and regulation of 
      human telomerase; however, the molecular basis for recruitment is not known. 
      Here, we have directly investigated the process of telomerase recruitment via 
      fluorescence in situ hybridization (FISH) and chromatin immunoprecipitation 
      (ChIP). We find that depletion of two components of the shelterin complex that is 
      found at telomeres--TPP1 and the protein that tethers TPP1 to the complex, 
      TIN2--results in a loss of telomerase recruitment. On the other hand, we find 
      that the majority of the observed telomerase association with telomeres does not 
      require POT1, the shelterin protein that links TPP1 to the single-stranded region 
      of the telomere. Deletion of the oligonucleotide/oligosaccharide binding fold 
      (OB-fold) of TPP1 disrupts telomerase recruitment. In addition, while loss of 
      TPP1 results in the appearance of DNA damage factors at telomeres, the DNA damage 
      response per se does not account for the telomerase recruitment defect observed 
      in the absence of TPP1. Our findings indicate that TIN2-anchored TPP1 plays a 
      major role in the recruitment of telomerase to telomeres in human cells and that 
      recruitment does not depend on POT1 or interaction of the shelterin complex with 
      the single-stranded region of the telomere.
FAU - Abreu, Eladio
AU  - Abreu E
AD  - Department of Biochemistry, University of Georgia, Athens, Georgia 30602, USA.
FAU - Aritonovska, Elena
AU  - Aritonovska E
FAU - Reichenbach, Patrick
AU  - Reichenbach P
FAU - Cristofari, Gael
AU  - Cristofari G
FAU - Culp, Brad
AU  - Culp B
FAU - Terns, Rebecca M
AU  - Terns RM
FAU - Lingner, Joachim
AU  - Lingner J
FAU - Terns, Michael P
AU  - Terns MP
LA  - eng
GR  - 232812/ERC_/European Research Council/International
GR  - F31 GM087949/GM/NIGMS NIH HHS/United States
GR  - R01 CA104676/CA/NCI NIH HHS/United States
GR  - F31GM087949/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100419
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (ACD protein, human)
RN  - 0 (POT1 protein, human)
RN  - 0 (Shelterin Complex)
RN  - 0 (TINF2 protein, human)
RN  - 0 (Telomere-Binding Proteins)
RN  - EC 2.7.7.49 (TERT protein, human)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Chromatin Immunoprecipitation
MH  - DNA Damage
MH  - HeLa Cells
MH  - Humans
MH  - Protein Binding
MH  - Protein Structure, Secondary
MH  - Protein Transport
MH  - Shelterin Complex
MH  - Telomerase/*metabolism
MH  - Telomere/*enzymology
MH  - Telomere-Binding Proteins/chemistry/deficiency/*metabolism
PMC - PMC2876666
EDAT- 2010/04/21 06:00
MHDA- 2010/06/18 06:00
PMCR- 2010/12/01
CRDT- 2010/04/21 06:00
PHST- 2010/04/21 06:00 [entrez]
PHST- 2010/04/21 06:00 [pubmed]
PHST- 2010/06/18 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - MCB.00240-10 [pii]
AID - 0240-10 [pii]
AID - 10.1128/MCB.00240-10 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2010 Jun;30(12):2971-82. doi: 10.1128/MCB.00240-10. Epub 2010 Apr 
      19.