The BUB3-BUB1 Complex Promotes Telomere DNA Replication

Feng Li, Hyeung Kim, Zhejian Ji, Tianpeng Zhang, Bohong Chen, Yuanlong Ge, Yang Hu, Xuyang Feng, Xin Han, Huimin Xu, Youwei Zhang, Hongtao Yu, Dan Liu, Wenbin Ma, Zhou Songyang

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Telomeres and telomere-binding proteins form complex secondary nucleoprotein structures that are critical for genome integrity but can present serious challenges during telomere DNA replication. It remains unclear how telomere replication stress is resolved during S phase. Here, we show that the BUB3-BUB1 complex, a component in spindle assembly checkpoint, binds to telomeres during S phase and promotes telomere DNA replication. Loss of the BUB3-BUB1 complex results in telomere replication defects, including fragile and shortened telomeres. We also demonstrate that the telomere-binding ability of BUB3 and kinase activity of BUB1 are indispensable to BUB3-BUB1 function at telomeres. TRF2 targets BUB1-BUB3 to telomeres, and BUB1 can directly phosphorylate TRF1 and promote TRF1 recruitment of BLM helicase to overcome replication stress. Our findings have uncovered previously unknown roles for the BUB3-BUB1 complex in S phase and shed light on how proteins from diverse pathways function coordinately to ensure proper telomere replication and maintenance. Telomeres and telomere-binding proteins form nucleoprotein structures that can present serious challenges during telomere DNA replication. Li et al. show that TRF2 targets the BUB1-BUB3 complex to telomeres during S phase and promotes telomere DNA replication. BUB1 phosphorylates TRF1 to promote recruitment of BLM helicase to overcome replication stress.

Original languageEnglish (US)
Pages (from-to)395-407.e4
JournalMolecular cell
Volume70
Issue number3
DOIs
StatePublished - May 3 2018

Keywords

  • BLM
  • BUB 3
  • BUB1
  • DNA replication
  • TRF1
  • TRF2
  • telomere
  • telomere length

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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