Sandbox Reserved 1103: Difference between revisions
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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>. | 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>. | ||
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>. | 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>. | ||
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>. | 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>. | ||
