TRF2 recruits ORC through TRFH domain dimerization

Mitsunori Higa, Tatsunori Kushiyama, Seiichiro Kurashige, Daisuke Kohmon, Kouki Enokitani, Satoko Iwahori, Nozomi Sugimoto, Kazumasa Yoshida, Masatoshi Fujita

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Telomeres are specialized chromatin structures that prevent the degradation and instability of the ends of linear chromosomes. While telomerase maintains long stretches of the telomeric repeat, the majority of telomeric DNA is duplicated by conventional DNA replication. A fundamental step in eukaryotic DNA replication involves chromatin binding of the origin recognition complex (ORC). In human cells, telomeric repeat binding factor 2 (TRF2) is thought to play a role in the recruitment of ORC onto telomeres. To better understand the mechanism of TRF2-mediated ORC recruitment, we utilized a lacO-LacI protein tethering system in U2OS cells and found that ectopically targeted TRF2, but not TRF1, can recruit ORC onto the lacO array. We further found that the TRF homology (TRFH) dimerization domain of TRF2, but not its mutant defective in dimerization, is sufficient for ORC and minichromosome maintenance (MCM) recruitment. Mutations impairing the dimerization also compromised ORC recruitment by full-length TRF2. Similar results were obtained using immunoprecipitation and GST pull-down assays. Together, these results suggest that dimerized TRF2 recruits ORC and stimulates pre-replication complex (pre-RC) formation at telomeres through the TRFH domain.

Original languageEnglish
Pages (from-to)191-201
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number1
Publication statusPublished - 01-01-2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


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