Cooperation of DNA-PKcs and WRN helicase in the maintenance of telomeric D-loops

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Rika Kusumoto-Matsuo, Patricia L Opresko, Dale Ramsden, Hidetoshi Tahara, Vilhelm A Bohr

Werner syndrome is an inherited human progeriod syndrome caused by mutations in the gene encoding the Werner Syndrome protein, WRN. It has both 3'-5' DNA helicase and exonuclease activities, and is suggested to have roles in many aspects of DNA metabolism, including DNA repair and telomere maintenance. The DNA-PK complex also functions in both DNA double strand break repair and telomere maintenance. Interaction between WRN and the DNA-PK complex has been reported in DNA double strand break repair, but their possible cooperation at telomeres has not been reported. This study analyzes thein vitro and in vivo interaction at the telomere between WRN and DNA-PKcs, the catalytic subunit of DNA-PK. The results show that DNA-PKcs selectively stimulates WRN helicase but not WRN exonuclease in vitro, affecting that WRN helicase unwinds and promotes the release of the full-length invading strand of a telomere D-loop model substrate. In addition, the length of telomeric G-tails decreases in DNA-PKcs knockdown cells, and this phenotype is reversed by overexpression of WRN helicase. These results suggest that WRN and DNA-PKcs may cooperatively prevent G-tail shortening in vivo.
Original languageEnglish
JournalAging
Volume2
Issue number5
Pages (from-to)274-84
Number of pages11
ISSN1945-4589
Publication statusPublished - 1 May 2010

    Research areas

  • Calcium-Binding Proteins, Cell Line, DNA, DNA Repair, Exodeoxyribonucleases, Humans, RecQ Helicases, Telomere, Werner Syndrome

ID: 33492192