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

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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)12234-12251
Number of pages18
JournalNucleic acids research
Volume49
Issue number21
DOIs
Publication statusPublished - Dec 2 2021

All Science Journal Classification (ASJC) codes

  • Genetics

Fingerprint

Dive into the research topics of 'TRF2-mediated ORC recruitment underlies telomere stability upon DNA replication stress'. Together they form a unique fingerprint.

Cite this