Chromosomal DNA ends shorten after each round of replication due to end-replication
problem and post replication processing. The ends of linear eukaryotic chromosomes are
capped and protected by protein-DNA complexes forming a structure called the telomere.
The telomere length is crucial as critically short telomeres activate the DNA damage response
pathway leading to cell senescence. The telomere is extended by a protein-RNA enzyme
complex with reverse transcriptase function named telomerase. The process by which
telomerase extends telomeres must be tightly regulated. Human telomerase is inactive in
normal human somatic cells but activated by various mechanisms in over 85~90% of cancer
cells. The aim of my work is to obtain high resolution structure of human telomerase complexes using cryo-EM.
I present biochemical and structural information of human telomerase complexes.