YLP motif-containing protein 1 plays a role in the reduction of telomerase activity during differentiation of embryonic stem cells by binding to the core promoter of TERT and controlling its down-regulation [].
The catalytic subunit of telomerase is structurally similar to retroviral reverse transcriptases, viral RNA polymerases and, to a lesser extent, the bacteriophage B-family DNA polymerases. Like its structural homologues, the core catalytic subunit of telomerase, TERT, contains the fingers, palm and thumb domains required for nucleic acid and nucleotide associations as well as catalysis. The four major TERT domains: the RNA binding domain (TRBD); the fingers domain, implicated in nucleotide binding and processivity; the palm domain, which contains the active site of the enzyme; and the thumb domain, implicated in DNA binding and processivity are organized into a ring configuration similar to that observed for the substrate-free enzyme. This is the thumb domain found in Tribolium castaneum telomerase catalytic subunit, TERT. Contacts between TERT and the DNA substrate are mostly mediated via backbone interactions with the thumb loop and helix. The thumb helix sits in the minor groove of the RNA-DNA heteroduplex, making extensive contacts with the phosphodiester backbone and the ribose groups of the RNA-DNA hybrid [, ].
Telomerase is an enzyme that, in certain cells, maintains the physical endsof chromosomes (telomeres) during replication. In somatic cells, replicationof the lagging strand requires the continual presence of an RNA primerapproximately 200 nucleotides upstream, which is complementary to thetemplate strand. Since there is a region of DNA less than 200 base pairsfrom the end of the chromosome where this is not possible, the chromosome iscontinually shortened. However, there is a surplus of repetitive DNA at the ends, the telomeres, that protects against the erosion of gene-encoding DNA.Telomerase is a ribonucleoprotein (RNP) that synthesises the telomeric DNArepeats. The telomerase RNA subunit provides the template for synthesis ofthese repeats. There are 2 protein components of the RNP: the catalyticsubunit is known as telomerase reverse transcriptase (TERT). The reversetranscriptase domain is located in the C-terminal region of the TERTpolypeptide and single amino acid substitutions in this region lead totelomere shortening and senescence [].Telomerase is not normally expressed in somatic cells and it has beensuggested that exogenous TERT may extend the lifespan of, or evenimmortalise, the cell. However, recent studies have shown that telomeraseactivity can be induced by a number of oncogenes []. Conversely, theoncogene c-myc can be activated in human TERT immortalised cells [].
