Sandbox Reserved 1103: Difference between revisions
From Proteopedia
Jump to navigationJump to search
Judith Weber (talk | contribs) No edit summary |
Judith Weber (talk | contribs) No edit summary |
||
| Line 34: | Line 34: | ||
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. | ||
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 | 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"/>. | ||
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> | 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> | ||
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>. | 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>. | ||
