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data supports a mechanism whereby telomerase deficiency and subsequent shortened telomeres initiate a DNA damage response and create a pro-oxidant environment, especially in Dyskeratosis Congenita cells carrying TINF2 mutations
telomerase elongates telomeres at a reduced frequency in TIN2-R282H heterozygous cells; this recruitment defect is further corroborated by examining the effect of this mutation on telomerase-telomere co-localization.
Our findings identify TINF2 as a mutant telomere gene in familial pulmonary fibrosis and suggest that infertility may precede the presentation of pulmonary fibrosis in a small subset of adults with telomere syndromes
A potential mitotic regulation of TIN2 by phosphorylation, is reported.
results suggest a link between telomeric proteins (TIN2)and metabolic control, providing an additional mechanism by which telomeric proteins regulate cancer and aging
Results suggests that the disruption of TIN2-TRF1 (show TERF1 Proteins) interaction may contribute to the severe dyskeratosis congenita phenotype observed in the context of the TIN2 truncation mutation.
The positive correlation between telomere length in dyskeratosis congenital and percent of LINE-1 methylation was restricted to TINF2 mutations.
Frameshift or nonsense mutations in TIN2 gene having very short telomeres are found in patients with dyskeratosis congenita.
Siah2 (show SIAH2 Proteins) acts as an E3 ligase to directly ubiquitylate TIN2 in vitro.
These results demonstrate the important roles that Sp1 (show PSG1 Proteins) and NF-kappaB (show NFKB1 Proteins) play in regulating the expression of the human telomere-binding protein TIN2.
Gene dosage reductions of Trf1 (show TERF1 Proteins) and/or Tin2 induce telomere DNA damage and lymphoma formation in aging mice.
demonstrated that cells expressing TIN2DeltaTPP1 instead of wild-type TIN2 phenocopy the POT1a (show POT1 Proteins),b knockout setting without showing additional phenotypes
shelterin protein TIN2 can protect chromosome ends as a TRF2 (show TERF2 Proteins)-tethered TIN2/TPP1 (show TPP1 Proteins)/POT1 (show POT1 Proteins) complex that lacks a physical connection to TRF1 (show TERF1 Proteins)
telomere shortening was accelerated in TIN2(+/DC) mTR (show MTR Proteins)(-/-) mice and MEFs compared with TIN2(+/+) mTR (show MTR Proteins)(-/-) controls, establishing that the TIN2(DC) telomere maintenance defect was not solely due to diminished telomerase action
Telomere protection by TPP1 (show TPP1 Proteins)/POT1 (show POT1 Proteins) requires tethering to TIN2.
TIN2 has a role independent of telomere length regulation that is essential for embryonic development and cell viability
This gene encodes one of the proteins of the shelterin, or telosome, complex which protects telomeres by allowing the cell to distinguish between telomeres and regions of DNA damage. The protein encoded by this gene is a critical part of shelterin\; it interacts with the three DNA-binding proteins of the shelterin complex, and it is important for assembly of the complex. Mutations in this gene cause dyskeratosis congenita (DKC), an inherited bone marrow failure syndrome.
TERF1-interacting nuclear factor 2
, TRF1-interacting nuclear protein 2
, TRF1-interacting nuclear factor 2