TRF2-mediated ORC recruitment underlies telomere stability upon DNA replication stress

Mitsunori Higa, Yukihiro Matsuda, Jumpei Fujii, Nozomi Sugimoto, Kazumasa Yoshida, Masatoshi Fujita

研究成果: ジャーナルへの寄稿学術誌査読

1 被引用数 (Scopus)

抄録

Telomeres are intrinsically difficult-to-replicate region of eukaryotic chromosomes. Telomeric repeat binding factor 2 (TRF2) binds to origin recognition complex (ORC) to facilitate the loading of ORC and the replicative helicase MCM complex onto DNA at telomeres. However, the biological significance of the TRF2-ORC interaction for telomere maintenance remains largely elusive. Here, we employed a TRF2 mutant with mutations in two acidic acid residues (E111A and E112A) that inhibited the TRF2-ORC interaction in human cells. The TRF2 mutant was impaired in ORC recruitment to telomeres and showed increased replication stress-associated telomeric DNA damage and telomere instability. Furthermore, overexpression of an ORC1 fragment (amino acids 244-511), which competitively inhibited the TRF2-ORC interaction, increased telomeric DNA damage under replication stress conditions. Taken together, these findings suggest that TRF2-mediated ORC recruitment contributes to the suppression of telomere instability.

本文言語英語
ページ(範囲)12234-12251
ページ数18
ジャーナルNucleic acids research
49
21
DOI
出版ステータス出版済み - 12月 2 2021

!!!All Science Journal Classification (ASJC) codes

  • 遺伝学

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