Cloning Components of Human Telomerase

Telomerase is an enzyme needed to maintain telomeres, and is therefore needed for the indefinite growth of cancer cells. An anti-telomerase drug might therefore be a good anti-tumor agent. To help in finding such drugs, two-hybrid and three-hybrid screens have been done in an attempt to identify new components of the telomerase complex. The two-hybrid screen yielded no new components. The three-hybrid screen yielded multiple interactors, but it is still not clear whether these are genuine components of telomerase. The most interesting of these is poly ADP-ribose polymerase PARP, which is known to be involved in DNA repair, and is a homolog of a protein known to function at telomeres. In addition, telomerase activity has been reconstituted in vitro. Finally, the role of a yeast telomerase component, Est1, was defined. Est1 is an RNA binding protein that binds the telomerase RNA, and helps bring it to the telomere. RNA binding proteins are also found in the telomerase complexes from other organisms, including mammals, and so the understanding of this yeast component may improve our understanding of human telomerase.