The Caenorhabditis elegans WRN helicase promotes double-strand DNA break repair by mediating end resection and checkpoint activation

Jin Sun Ryu, Hyeon Sook Koo

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9 Citations (Scopus)

Abstract

The protein associated with Werner syndrome (WRN), is involved in DNA repair, checkpoint activation, and telomere maintenance. To better understand the involvement of WRN in double-strand DNA break (DSB) repair, we analyzed the combinatorial role of WRN-1, the Caenorhabditis elegans WRN helicase, in conjunction with EXO-1 and DNA-2 nucleases. We found that WRN-1 cooperates with DNA-2 to resect DSB ends in a pathway acting in parallel to EXO-1. The wrn-1 mutants show an aberrant accumulation of replication protein A (RPA) and RAD-51, and the same pattern of accumulation is also observed in checkpoint-defective strains. We conclude that WRN-1 plays a conserved role in the resection of DSB ends and mediates checkpoint signaling, thereby influencing levels of RPA and RAD-51.

Original languageEnglish
Pages (from-to)2155-2166
Number of pages12
JournalFEBS Letters
Volume591
Issue number14
DOIs
Publication statusPublished - 2017 Jul 1

Bibliographical note

Funding Information:
The wild-type Bristol N2, wrn-1(gk99), him-6(e1104), and him-6(e1423) were acquired from the C. elegans Genetics Center (St Paul, MN, USA), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). We thank Dr. Marcel Tijsterman (Leiden University Medical Center, The Netherlands) for exo-1(tm1842) mutant. This work was supported by Basic Science Research program through the National Research Foundation of Korea (NRF) grant funded by the Ministry of Education (No. 2014R1A1A2-057049) and by an NRF grant funded by the Ministry of Education, Science and Technology of Korea (No. 2012-029610) to HSK. The work was also supported in part by Brain Korea 21 PLUS program.

Publisher Copyright:
© 2017 Federation of European Biochemical Societies

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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