• Telomeres are repetitive nucleotide sequences located at the termini of linear chromosomes of most eukaryotic organisms.• Its name is derived from the Greek nouns telos =end and merοs = part’.• Most prokaryotes do not have telomeres.
TELOMERES Repetitive DNA sequence (TTAGGG in vertebrates) Specialized proteinsForm a capped end structure
• Telomere specific proteins, eg. TRF1 & TRF2 bind to the repeat sequence and protect the ends.• Without these proteins, telomeres are acted upon by DNA repair pathways leading to chromosomal fusions.
• While replicating DNA, the eukaryotic DNA replication enzymes cannot replicate the sequences present at the ends of the chromosomes .• Hence, these sequences and the information they carry may get lost.• Telomeres "cap" the end-sequences and themselves get lost in the process of DNA replication.
Telomeres are the ends ofchromosomes Protect ends Maintain length
THE END REPLICATION PROBLEM RNA primer near end of the chromosome on lagging strand can’t be replaced with DNA since DNA polymerase must add to a primer sequence.
TELOMERASE• Telomeric sequence is maintained by a special enzyme called telomerase.• Specialized reverse transcriptase.• Carries its own template RNA , which is complementary to telomeric repeat sequences.
Telomerase "replenishes" the telomere "cap" of the DNA
• In most multicellular eukaryotic organisms, telomerase is active only in germ cells, stem cells, and certain white blood cells.
•Many experiments haveshown that there is a directrelationship betweentelomeres and aging, and thattelomerase has the ability toprolong life and cell division.
• Most somatic cells do not have sufficiently high levels of telomerase to maintain the length of their telomeres for an indefinite number of cell divisions.• Consequently, telomeres gradually shorten as cells age.• This shortening eventually leads to cell death or senescence.
• Cancer cells express abnormally high levels of telomerase, allowing them to continue dividing indefinitely.