telomeric repeat-binding factor 2; TTAGGG repeat-binding factor 2; telomeric DNA-binding protein (TERF2 TRBF2 TRF2)
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Function
- binds the telomeric double-stranded 5'-TTAGGG-3' repeat & plays a central role in telomere maintenance & protection against end-to-end fusion of chromosomes
- in addition to its telomeric DNA-binding role, required to recruit a number of factors & enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 & DCLRE1B/apollo
- component of the shelterin complex (telosome)
- 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 & repair
- required both to recruit DCLRE1B/apollo to telomeres & 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 & TOP2B) needed for telomere replication during fork passage & prevent aberrant telomere topology
- recruits TERF2IP/RAP1 to telomeres, thereby participating in repressing homology-directed repair (HDR), which can affect telomere length
- phosphorylated upon DNA damage, probably by ATM or ATR
- interacts with TERF2IP
- interacts with NBN
- interacts with SLX4/BTBD12
- interacts with DCLRE1B/apollo & TERF2IP/RAP1
Structure
- homodimer
- the TRFH dimerization region mediates the interaction with DCLRE1B/apollo but not TINF2
- contains 1 HTH myb-type DNA-binding domain
Compartment
- nucleus, chromosome, telomere
- colocalizes with telomeric DNA in interphase cells & is located at chromosome ends during metaphase
Alternative splicing
named isoforms=2
Expression
- ubiquitous
- highly expressed in spleen, thymus, prostate, uterus, testis, small intestine, colon & peripheral blood leukocytes