KASHMEERA.N.AKASHMEERA.N.A

III SEM MSc ZOOLOGYIII SEM MSc ZOOLOGY

ROLL NO : 37ROLL NO : 37

CHRIST COLLEGECHRIST COLLEGE

WHAT ARE TELOMERES ?WHAT ARE TELOMERES ?

Telomeres are the ends of chromosomes

• Telomeres are repetitive nucleotide sequences Telomeres are repetitive nucleotide sequences located at the termini of linear chromosomes located at the termini of linear chromosomes of most eukaryotic organisms.of most eukaryotic organisms.

• Its name is derived from the Greek nouns Its name is derived from the Greek nouns telos ='end' and merοs = 'part’. telos ='end' and merοs = 'part’.

• Most prokaryotes do not have telomeres. Most prokaryotes do not have telomeres.

Repetitive DNA sequenceRepetitive DNA sequence(TTAGGG in vertebrates)(TTAGGG in vertebrates)

Specialized proteinsSpecialized proteins

Form a 'capped' end structureForm a 'capped' end structure

TELOMERESTELOMERES

• Telomere specific proteins, eg. TRF1 & TRF2 Telomere specific proteins, eg. TRF1 & TRF2 bind to the repeat sequence and protect the bind to the repeat sequence and protect the ends.ends.

• Without these proteins, telomeres are acted Without these proteins, telomeres are acted upon by DNA repair pathways leading to upon by DNA repair pathways leading to chromosomal fusions.chromosomal fusions.

• While replicating DNA, the eukaryotic DNA While replicating DNA, the eukaryotic DNA replication enzymes cannot replicate the replication enzymes cannot replicate the sequences present at the ends of the sequences present at the ends of the chromosomes .chromosomes .

• Hence, these sequences and the information Hence, these sequences and the information they carry may get lost.they carry may get lost.

• Telomeres "cap" the end-sequences and Telomeres "cap" the end-sequences and themselves get lost in the process of DNA themselves get lost in the process of DNA replication.replication.

Telomeres are the ends of chromosomes

Protect ends Maintain length

THE END REPLICATION PROBLEMTHE END REPLICATION PROBLEM

RNA primer near RNA primer near end of the end of the chromosome on chromosome on lagging strand can’t lagging strand can’t be replaced with be replaced with DNA since DNA DNA since DNA polymerase must polymerase must add to a primer add to a primer sequence.sequence.

TELOMERASETELOMERASE

• Telomeric sequence is maintained by a special Telomeric sequence is maintained by a special enzyme called telomerase.enzyme called telomerase.

• Specialized Specialized reverse transcriptase.reverse transcriptase.

• Carries its own template RNA , which is Carries its own template RNA , which is complementary to telomeric repeat sequences.complementary to telomeric repeat sequences.

Telomerase "replenishes" the telomere "cap" of the DNA Telomerase "replenishes" the telomere "cap" of the DNA

• In most multicellular eukaryotic organisms, In most multicellular eukaryotic organisms, telomerase is active only in germ cells, stem telomerase is active only in germ cells, stem cells, and certain white blood cells. cells, and certain white blood cells.

HOW TELOMERASE WORK ?HOW TELOMERASE WORK ?

MECHANISM OF TELOMERASE ACTIONMECHANISM OF TELOMERASE ACTION

TetrahymenaTetrahymena

Model organism used in telomere & telomerase research.Model organism used in telomere & telomerase research.

MECHANISM OF TELOMERASE ACTIONMECHANISM OF TELOMERASE ACTION

Removal of the RNA Removal of the RNA primer leaves an overhanging 3' end of primer leaves an overhanging 3' end of chromosomal DNA, which can chromosomal DNA, which can form loops at the ends of eukaryotic form loops at the ends of eukaryotic chromosomes chromosomes

CLINICAL ASPECTSCLINICAL ASPECTS

•Many experiments have Many experiments have shown that there is a direct shown that there is a direct relationship between relationship between telomeres and aging, and that telomeres and aging, and that telomerase has the ability to telomerase has the ability to prolong life and cell division.prolong life and cell division.

• Most somatic cells do not have sufficiently Most somatic cells do not have sufficiently high levels of telomerase to maintain the high levels of telomerase to maintain the length of their telomeres for an indefinite length of their telomeres for an indefinite number of cell divisions. number of cell divisions.

• Consequently, telomeres gradually shorten as Consequently, telomeres gradually shorten as cells age.cells age.

• This shortening eventually leads to cell death This shortening eventually leads to cell death or senescence. or senescence.

• Cancer cells express abnormally high levels of Cancer cells express abnormally high levels of telomerase, allowing them to continue dividing telomerase, allowing them to continue dividing indefinitely. indefinitely.