Telomere-binding protein connects with telomere
TERF1
TERF1 is present during all stages of the cell cycle, acting as a negative regulator in tandem with TERF2 while in contrast to telomerase. Its main function seems to be observed in controlling the telomere lengths via inhibition of telomerase. Removal of TERF1 will therefore lead to an increase in telomere length. TERF1 may reduce the accessibility of telomerase towards the end of the DNA length, which results in its inhibition. There may be potential post-translation modifications of TERF1 by adding ribose to induce regulation of telomerase. After the lengthening of the telomere, TERF1 reassembles to form an inaccessible T-loop structure.It has homology to the Myb transcription factors as the protein-DNA complex requires both Myb repeats. TERF1 binds near the N-terminus on a highly conserved domain to form a homodimer interaction. Since TERF1 bends the telomeric site, it may be a critical step in properly functioning telomeres to maintain its length. TERF1 also serves to prevent problematic secondary structures from hindering progression by interacting with helicase for unobstructed unwinding.TERF2
TERF2 is a homolog to TERF1, exhibiting many functional and biochemical similarities. TERF2, like TERF1 has some relation to the Myb DNA binding motif. It serves as a secondary negative regulator, as overexpression of TERF2 produces a shortened telomere. TERF2 may also conceal the ends of the telomere in order to prevent detection from degradation. There is more conservation across species in TERF2 possibly due to higher risk of senescence when mutated.TERF2 binds directly to the DNA sequence, forming a T-loop structure. Therefore, TERF2 plays a role in inducing loop formation by folding the 3’ TTAGGG sequence back into the duplex sequence. When removed, degradation of telomeric 3’ overhangs can be observed. However, this requires the work of excision repair exonuclease ERCC1/XPF so inhibition of TERF2 alone may not necessarily lead to immediate shortening. Upon deletion of TERF2, there is co-localization with TERF1 with the association of DNA damage response factors. Under regular cell conditions, TERF2 is known to suppress the ATM pathway, however, the mechanisms of which, are currently unclear.