The RIF1-Long splice variant promotes G1 phase 53BP1 nuclear bodies to protect against replication stress

Lotte P Watts, Toyoaki Natsume, Yuichiro Saito, Javier Garzon, Qianqian Dong, Lora Boteva, Nick Gilbert, Masato T Kanemaki, Shin-Ichiro Hiraga, Anne D Donaldson

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Human cells lacking RIF1 are highly sensitive to replication inhibitors, but the reasons for this sensitivity have been enigmatic. Here we show that RIF1 must be present both during replication stress and in the ensuing recovery period to promote cell survival. Of two isoforms produced by alternative splicing, we find that RIF1-Long alone can protect cells against replication inhibition, but RIF1-Short is incapable of mediating protection. Consistent with this isoform-specific role, RIF1-Long is required to promote the formation of the 53BP1 nuclear bodies that protect unrepaired damage sites in the G1 phase following replication stress. Overall, our observations show that RIF1 is needed at several cell cycle stages after replication insult, with the RIF1-Long isoform playing a specific role during the ensuing G1 phase in damage site protection.
Original languageEnglish
Article numbere58020
Number of pages26
JournaleLife
Volume9
Early online date3 Nov 2020
DOIs
Publication statusPublished - 3 Nov 2020

Keywords

  • RIF1
  • DNA replication
  • DNA replication stress
  • Splicing
  • replication stress
  • cell biology
  • chromosomes
  • splicing
  • human
  • gene expression

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