TERF2 antibody

Background of TERF2 antibody

Human telomeres are composed of long sequences of TTAGGG repeats that form a nucleoprotein complex required for the stability, protection and replication of chromosome ends. One component of such human telomeres is the TTAGGG repeat binding factor 1 (TRF1), a ubiquitously expressed protein, related to the proto-oncogene Myb, that is present at telomeres throughout the cell cycle. Natural chromosomal ends are stabilized by proteins that bind duplex telomeric DNA repeats known as TTAGGG repeat Factors. Two independent studies isolated two proteins a 65kDa protein that bind to telomeric DNA and second open reading frame coding for 69kDa protein that binds to telomeric repeat DNA in vitro. These proteins are expressed in HeLa cells and together called TRF2. Affinity purified antibodies to TRF2 binds ro telomeres of intact human chromosomes (1). A stretch of 60 amino acids located at the C-terminal end of the protein is critical for the DNA binding. The region exhibit close homology with Myb repeats and is conserved in several proteins two of which are known to bind telomric repeat sequences. Both TRF1 and TRF2 are ubiquitously expressed, bound specifically to duplex TTAGGG repeats are localized to all human telomeres in metaphase chromosomes. TTAGGG repeat factor 2 (TRF2), is thought to protect telomere ends by remodeling them into T-loops.
Functionally TRF1 controls the telomere length and is proposed to be a telomerase inhibitor acting in cis to limit the telopere elongation of individual chromosome ends. TRF1 has similar architectural structure as of TRF2 both have a Myb motif and a large TRF1-related dimirization domain near its N-terminus. The dimerization domain of TRF1 and TRF2 do not interact suggesting that these two proteins exist as homodimmers. TRF2 specifically interacts with telomeric ss/ds DNA junctions and binding is sensitive to the sequence of the 3’, guanine-strand (G-strand) overhang and double-stranded DNA sequence at the junction. Association of TRF2 with DNA junctions hinders cleavage by exonuclease T (2). TRF1 and TRF2 differs at amino terminal end of the proteins, TRF2 being basic rather than acidic as in TRF1 protein (3). The TRF2 also plays a key role in protective activity of telomerase, prevent the end-to-end fusion of telomeres and are implicated in senescence in primary human cells due to shortening of the telomeres.