Telomerase activity and stabilization by a loop

Two features characterize the telomere: telomerase
activity to compensate for replication-related
loss of nucleotides at the chromosome
ends and telomeric DNA loop formation to stabilize
the chromosome ends. Telomerase is a
modified reverse transcriptase consisting of
protein and about 450 nucleotides of RNA. Near
the RNA 5' end are sequences complementary to
telomeric DNA repeat sequences. A short nucleotide
sequence of this RNA pairs with terminal
DNA sequences. The adjacent RNA nucleotides
provide the template for adding nucleotides
to the 3' end of the chromosome. After
telomerase has extended the 3' (G-rich) strand,
a new Okazaki fragment can be synthesized at
the 5' strand by DNA polymerase. Griffith et al.
(1999) have shown that telomeric duplex DNA
forms a loop (t-loop), thus avoiding the ”sticky
end” problem. The loop formation is mediated
by the two related proteins TRF1 (telomeric repeat-
binding factor) and TRF2, which bind to
mammalian telomere repeats, and the loop is
anchored by the insertion of the G-strand overhang
(see B) into a proximal segment of duplex
telomeric DNA.