MRNIP/C5orf45 Interacts with the MRN Complex and Contributes to the DNA Damage Response

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  • Christopher J Staples
    University of Sheffield
  • Giancarlo Barone
    University of Sheffield
  • Katie N Myers
    University of Sheffield
  • Anil Ganesh
    University of Sheffield
  • Ian Gibbs-Seymour
    University of Oxford
  • Abhijit A Patil
    University of Sheffield
  • Ryan D Beveridge
    University of Sheffield
  • Caroline Daye
    University of Sheffield
  • Richard Beniston
    University of Sheffield
  • Sarah Maslen
    Mass Spectrometry Group, Cambridge
  • Ivan Ahel
    University of Oxford
  • J Mark Skehel
    Mass Spectrometry Group, Cambridge
  • Spencer J Collis
    University of Sheffield

Through an RNAi-based screen for previously uncharacterized regulators of genome stability, we have identified the human protein C5orf45 as an important factor in preventing the accumulation of DNA damage in human cells. Here, we functionally characterize C5orf45 as a binding partner of the MRE11-RAD50-NBS1 (MRN) damage-sensing complex. Hence, we rename C5orf45 as MRNIP for MRN-interacting protein (MRNIP). We find that MRNIP is rapidly recruited to sites of DNA damage. Cells depleted of MRNIP display impaired chromatin loading of the MRN complex, resulting in reduced DNA end resection and defective ATM-mediated DNA damage signaling, a reduced ability to repair DNA breaks, and radiation sensitivity. Finally, we show that MRNIP phosphorylation on serine 115 leads to its nuclear localization, and this modification is required for MRNIP's role in promoting genome stability. Collectively, these data reveal that MRNIP is an important component of the human DNA damage response.


  • Journal Article
Original languageEnglish
Pages (from-to)2565-75
Number of pages11
Issue number10
Early online date25 Aug 2016
Publication statusPublished - 6 Sep 2016

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