SHELTERIN COMPLEX

Protein-protein interactions. Control nucleolytic processing of 5’ strand (remarkably precise

– AATCCCAATC-5’). Concept: protect chromosome ends by actively changing architecture of
telomeric DNA

Complexes found in other eukaryotes:

TRF – fission yeast and trypanosomes

POT1- nearly all

RAP1 – fungi

TPP1 and TIN2 – ONLY in vertebrates

Fig. 2 The shelterin complex, composed of TRF1, TRF2, TIN1, POT1, TPP1, and RAP1
stabilizes the telomere and prevents telomere overhang exposure. Tankyrase causes dissociation
of shelterin through PARsylation of TRF1, leading to telomere overhang disruption. T-oligo is
then able to bind the shelterin complex and maintain exposure of the telomere overhang which
leads to either telomere elongation or DNA damage responses including apoptosis or
differentiation.
 TELOMERASE AS AN AGENT TO EXTEND CELLULAR LIFESPAN
Telomere loss is thought to control entry into senescence. Human telomeres consist of repeats of
the sequence TTAGGG/CCCTAA at chromosome ends. Telomerase is active in germline cells
but it is not expressed in most human somatic tissues, and telomere length is significantly shorter
in the latter. Telomere Hypothesis of Cellular Aging proposes that cells become senescent
when progressive telomere shortening during each division produces a threshold telomere length
Telomerase activity in cells can be reconstituted by overexpression of hTERT, frequently
resulting in extension of replicative life span or immortalization.

Does the gradual shortening of telomeres coincide with the long-term aging of man?

Telomere length shortens with age. Progressive shortening of telomeres leads to senescence,

apoptosis, or oncogenic transformation of somatic cells, affectingthe health and lifespan of an
individual. The rate of telomere shortening can be either increased or decreased by specific
lifestyle factors.

Telomeres are the specialized repetitive DNA sequences at the ends of the linear
chromosomes, and associated proteins, that serve to maintain the integrity of the chromosomes.
Telomerase is a ribonucleoprotein DNA polymerase complex that maintains telomere length.
The complex comprises the protein telomerase reverse.