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TINF2 is one of the nine identified genes that when mutated are related to the Dyskeratosis congenita, the others being [https://en.wikipedia.org/wiki/Dyskerin DKC1],[https://en.wikipedia.org/wiki/Telomerase_RNA_component TERC],[https://en.wikipedia.org/wiki/Telomerase_reverse_transcriptase TERT], NOP10, NHP2, C16orf57, TCAB1 and [https://en.wikipedia.org/wiki/Poly(A)-specific_ribonuclease PARN]. TIN2 mutations are imply in several different mechanims.
TINF2 is one of the nine identified genes that when mutated are related to the Dyskeratosis congenita, the others being [https://en.wikipedia.org/wiki/Dyskerin DKC1],[https://en.wikipedia.org/wiki/Telomerase_RNA_component TERC],[https://en.wikipedia.org/wiki/Telomerase_reverse_transcriptase TERT], NOP10, NHP2, C16orf57, TCAB1 and [https://en.wikipedia.org/wiki/Poly(A)-specific_ribonuclease PARN]. TIN2 mutations are imply in several different mechanims.
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The majority of identified TIN2 dyskeratosis congenita mutations cluster is a highly conserved 30-amino-acid region near the ends of its TRF1 binding domain <ref>PMID: 15316005 </ref>. A disruption of this domain causes a loss of TRF1 binding to TIN2, resulting in a telomeric instability<ref>PMID: 18252230 </ref>.
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The majority of identified TIN2 dyskeratosis congenita mutations cluster is a highly conserved 30-amino-acid region near the ends of its TRF1 binding domain <ref>PMID: 15316005 </ref>. A disruption of this domain causes a loss of TRF1 binding to TIN2, resulting in a telomeric instability <ref name="doc2"/>.
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Another proposal is that TIN2 helps TPP1, another component of the shelterin complex, in the recruitment of telomerase through an unknown mechanism that is disrupted by the TIN2 dyskeratosis congenita mutations, leading once again to a telomeric instability <ref>PMID: 18252230 </ref>.
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Another proposal is that TIN2 helps TPP1, another component of the shelterin complex, in the recruitment of telomerase through an unknown mechanism that is disrupted by the TIN2 dyskeratosis congenita mutations, leading once again to a telomeric instability <ref name="doc2"> PMID: 18252230</ref>
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Finally, TIN2 seems to regulate the effect of the [https://en.wikipedia.org/wiki/Tankyrase tankyrase 1], an poly ADP-ribose polymerase, by stabilising the formation of a TIN2–tankyrase 1–TRF1 complex. This prevent the binding of TRF1 to the telomere ends. In the case of amino acid mutations in TIN2 this might act by the same mechanism as a knock-down and leave telomere ends permanently unprotected, causing a shortening of telomere length <ref>PMID: 19419704 </ref>.
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Moreover,TIN2 seems to regulate the effect of the [https://en.wikipedia.org/wiki/Tankyrase tankyrase 1], a poly ADP-ribose polymerase, by stabilising the formation of a TIN2–tankyrase 1–TRF1 complex. The formation of this complex stops the binding of TRF1 to the ends of telomeres. Another cause of the disease can be amino acids mutations in TIN2. There are different types of mutations involved. There are some that block the formation of the TIN2-tankyrase 1-TRF1 complex. This let TRF1 fully available to inhibitit the addition of telomeres units to telomeres ends, which is problematic during period of rapid cell growth like embryogenesis. Also, when TRF1 binds to telomeres, it recruits a protein called POT1 and form a complex with it. It's a complex that blocks access to telomerase and protects the ends of telomeres. And so, there are amino acids mutations of TIN2 that prevent TRF1 binding to telomeres when needed, an so also prevent the protection of telomeres ends that can be the target of non-specific degradation. Thus leading to telomeres shortening. <ref>PMID: 19419704 </ref>.
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=== Revesz syndrome ===
=== Revesz syndrome ===
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Revesz syndrome is characterised by bone marrow hypoplasia, nail dystrophy, growth retardation, exudative retinopathy, severe aplastic anemia <ref>PMID: 17901676 </ref>. Revesz syndrome also appears to be part of the DKC disease spectrum. Patients with Revesz syndrome have presented with heterozygous mutations in TINF2 gene which is located on chromosome 14q12 <ref>PMID: 18252230 </ref>.
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Revesz syndrome is characterised by bone marrow hypoplasia, nail dystrophy, growth retardation, exudative retinopathy, severe aplastic anemia <ref>PMID: 17901676 </ref>. Revesz syndrome also appears to be part of the DKC disease spectrum. Patients with Revesz syndrome have presented with heterozygous mutations in TINF2 gene which is located on chromosome 14q12 <ref name="doc2"/>.
== References ==
== References ==
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{{Wikipedia|TERF1}}
{{Wikipedia|TERF1}}
{{Wikipedia|TINF2}}
{{Wikipedia|TINF2}}
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{{Wikipedia|Shelterin}
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{{Wikipedia|Shelterin}}

Current revision

TRF1 TRFH domain and TIN2 peptide complex, pdb=3BQO

The TRFH (Telomeric Repeat Factor Homology) is a domain which is in the centre of the TRF1(Telomeric Repeat-Binding Factor) and of about 200 amino acids.In humans TERF1 is encoded by the TERF1 gene. TIN2(TERF1-interacting Nuclear Factor) is a protein encoded in humans by the TINF2 gene that can bind to TRFH TRF1.

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