TRF2 Positive Control

This gene encodes a telomere specific protein, TERF2, which is a component of the telomere nucleoprotein complex. This protein is present at telomeres in metaphase of the cell cycle, is a second negative regulator of telomere length and plays a key role in the protective activity of telomeres. While having similar telomere binding activity and domain organization, TERF2 differs from TERF1 in that its N terminus is basic rather than acidic. [provided by RefSeq, Jul 2008]

TRF2: Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3' single- stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair. Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo. Preferentially binds to positive supercoiled DNA. Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology- directed repair (HDR), which can affect telomere length. Homodimer. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP/RAP1, ACD and POT1. Interacts with TERF2IP. Interacts with NBN. Interacts with SLX4/BTBD12. Interacts with DCLRE1B/Apollo and TERF2IP/RAP1; the interaction is direct. Ubiquitous. Highly expressed in spleen, thymus, prostate, uterus, testis, small intestine, colon and peripheral blood leukocytes. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: DNA-binding; DNA repair, damage

Chromosomal Location of Human Ortholog: 16q22.1

Cellular Component: chromosome, telomeric region; cytoplasm; Golgi apparatus; Mre11 complex; nuclear chromosome, telomeric region; nuclear telomere cap complex; nucleoplasm; nucleus

Molecular Function: double-stranded telomeric DNA binding; protein binding; protein C-terminus binding; protein homodimerization activity; telomerase activity; telomeric DNA binding

Biological Process: cell cycle; negative regulation of telomere maintenance; negative regulation of telomere maintenance via recombination; negative regulation of telomere maintenance via semi-conservative replication; positive regulation of nitric-oxide synthase activity; positive regulation of telomere maintenance; protection from non-homologous end joining at telomere; regulation of telomere maintenance; regulation of telomere maintenance via telomerase; telomere capping; telomere maintenance; telomere maintenance via telomerase; telomeric loop formation