期刊
AGING-US
卷 2, 期 5, 页码 274-284出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.100141
关键词
RecQ; WRN; DNA-PKcs; telomere; aging; DNA repair
资金
- Japan Society For the Promotion of Science (Japan)
- NIH, National Institute on Aging [CA84442, ES0515052]
- Ministry of Education, Culture, Sports, Science and Technology of Japan [20014015]
- Grants-in-Aid for Scientific Research [20014015] Funding Source: KAKEN
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 the in 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.
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