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

研究成果: ジャーナルへの寄稿学術誌査読

12 被引用数 (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.

ジャーナルBiochimica et Biophysica Acta - Molecular Cell Research
出版ステータス出版済み - 1月 1 2017

!!!All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞生物学


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