Ribosomal protein S3 is a novel negative regulator of non-homologous end joining repair of DNA double-strand breaks

Yong Jun Park, Tae Sung Kim, Eun Ho Kim, Hag Dong Kim, Joon Kim

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

DNA double-strand breaks (DSBs) are one of the most serious types of DNA damage. However, multiple repair pathways are present in cells to ensure rapid and appropriate repair of DSBs. Pathway selection depends on several factors including cell type, cell cycle phase, and damage severity. Ribosomal protein S3 (rpS3), a component of the 40S small ribosomal subunit, is a multi-functional protein primarily involved in protein synthesis. rpS3 is also involved in the mediation of various extra-ribosomal pathways, including DNA damage processing and the stress response. Here, we report that rpS3 is a novel negative regulator of non-homologous end joining (NHEJ)-mediated repair of DSBs. We found that rpS3 interacts with the Ku heterodimers of the DNA-dependent protein kinase (DNA-PK) complex and slows down NHEJ ligation reactions, ultimately triggering p53-dependent cell death following treatment with high-dose ionizing radiation. After DSB formation, DNA-PK phosphorylates rpS3, which consequently reduces the binding of rpS3 to the Ku complex. We hypothesized that rpS3 may play a role in DSB repair by repressing NHEJ, while inducing other repair pathways, and by initiating DSB-induced cell death in response to severe DNA damage.

Original languageEnglish
Pages (from-to)8102-8113
Number of pages12
JournalFASEB Journal
Volume34
Issue number6
DOIs
Publication statusPublished - 2020 Jun 1

Bibliographical note

Funding Information:
This work was supported by National Research Foundation of Korea (NRF) Grants 2017R1E1A1A01074101 and Korea University Grant 2019S1A5A2A03050121.

Publisher Copyright:
© 2020 Federation of American Societies for Experimental Biology

Keywords

  • DNA-PK
  • Ku
  • NHEJ
  • extra-ribosomal function
  • rpS3

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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