Telomere Telomerase DNA Damage Stem Cell Biology Diagrams 1. Telomere structure and maintenance 1) Telomeric DNA and G-quadruplex. Telomeres are comprised of repeat sequences and bound by multiple telomeric interacting proteins. In mammalian cells, telomere DNA contains double-stranded tandem repeats of TTAGGG followed by terminal 3โฒ G-rich single-stranded overhangs. Because NHEJ is repressed in mitosis 65, and TRF2 remains bound to deprotected mitotic telomeres to directly inhibit end-joining upon mitotic exit 29, there is no risk of telomere fusions from MAD
Given that nuclear DNA cannot be fully replicated during mitosis (i.e. end replication problem), telomeres shorten with each round of cell division, unless acted upon by different telomere Telomeres are the physical ends of eukaryotic chromosomes. They protect chromosome ends from DNA degradation, recombination, and DNA end fusions, and they are important for nuclear architecture. Telomeres provide a mechanism for their replication by semiconservative DNA replication and length maintenance by telomerase. The maintenance of telomere length is a prerequisite for the continuous division of cells, so telomerase is more active in cells that need to sustain division, such as tumor cells, stem cells, etc. And telomerase is specifically designed as a reverse transcriptase to resist telomere shortening.
Replication of Telomeres and the Regulation of Telomerase Biology Diagrams
Dyskerin is a highly conserved, nucleolar RNA-binding protein with established roles in small nuclear ribonucleoprotein biogenesis, telomerase and telomere maintenance and precursor rRNA processing. Telomerase is functional during S phase and the bulk of rRNA maturation occurs during G 1 and S phases; both processes are inactivated during mitosis. MUS81 operates in distinct phases of the cell cycle, during S phase, MUS81 forms a complex with EME2, crucial for fork cleavage and telomere maintenance in cells dependent on the alternative Interestingly, ALT cancer cells and normal aged cells have another feature in common: persistent telomere cohesion. Thus, similar to tankyrase-depleted or TRF1-mutated cells, telomeres of aged and ALT cells are persistently cohered into mitosis. 15, 25, 26, 27 Persistent cohesion is a direct consequence of telomere shortening; it can be counteracted by introduction of telomerase into aged or
