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

Abstract

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.

• Authors: Rika Kusumoto-Matsuo, Patricia L Opresko, Dale Ramsden, Hidetoshi Tahara, Vilhelm A Bohr
• Journal: Aging (Aging (Albany NY)) Vol. 2 Issue 5 Pg. 274-84 (May 2010) ISSN: 1945-4589 [Electronic] United States
• PMID: 20519774 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• CIB1 protein, human
• Calcium-Binding Proteins
• DNA
• Exodeoxyribonucleases
• RecQ Helicases
• WRN protein, human
• Werner Syndrome Helicase

Topics

• Calcium-Binding Proteins (genetics, metabolism)
• Cell Line
• DNA (genetics, metabolism)
• DNA Repair
• Exodeoxyribonucleases (genetics, metabolism)
• Humans
• RecQ Helicases (genetics, metabolism)
• Telomere (genetics, metabolism)
• Werner Syndrome (genetics, metabolism)
• Werner Syndrome Helicase