Bio-X Affiliated Faculty

The Artandi lab is interested in unraveling the molecular and cellular mechanisms according to which telomeres and telomerase modulate stem cell function and carcinogenesis.

Telomeres, the nucleoprotein structures that cap the ends of eukaryotic chromosomes, serve essential roles in preventing checkpoint activation and in maintaining chromosomal stability. Telomeres are composed of G-rich nucleotide repeats bound by a complex array of proteins that help stabilize formation of a looped and protected chromosomal end. Telomeres shorten progressively in humans, both in cultured cells and in certain tissues with advancing age. Telomeres shorten because DNA polymerase cannot fully replicate the lagging strand - the end-replication problem - and because certain stem/progenitor cell compartments express inadequate levels of telomerase, the reverse transcriptase that synthesizes telomeric repeats. Telomerase consists of two essential components: an RNA subunit, TERC, and a protein catalytic subunit, TERT. TERT is a reverse transcriptase that binds TERC and synthesizes telomeres by copying the telomere repeat sequences encoded in the TERC template. Overexpression of TERT in primary human cells is sufficient to extend telomeres and allow unlimited proliferation. In addition to its role in telomere maintenance, TERT can activate resting stem cells through an independent pathway.