DOI: 10.1046/j.1365-2443.2001.00433.x. Werner helicase relocates into nuclear foci in response to DNA damaging agents and co‐localizes with RPA and Rad51

Werner helicase relocates into nuclear foci in response to DNA damaging agents and co‐localizes with RPA and Rad51

10.1046/j.1365-2443.2001.00433.x

Crossref journal-article

Wiley

Genes to Cells (311)

Abstract

BackgroundWerner syndrome (WS) is an autosomal recessive disorder with many features of premature ageing. Cells derived from WS patients show genomic instability, aberrations in the S‐phase and sensitivity to genotoxic agents. The gene responsible for WS (WRN) encodes a DNA helicase belonging to the RecQ helicase family. Although biochemical studies showed that the gene product of WRN (WRNp) interacts with proteins that participate in DNA metabolism, its precise biological function remains unclear.ResultsUsing immunocytochemistry, we found that WRNp forms distinct nuclear foci in response to DNA damaging agents, including camptothecin (CPT), etoposide, 4‐nitroquinolin‐N‐oxide and bleomycin. The presence of aphidicolin inhibited CPT‐induced WRNp foci strongly but not bleomycin‐induced foci. These WRNp foci overlapped with the foci of replication protein A (RPA) almost entirely and with the foci of Rad51 partially, implicating cooperative functions of these proteins in response to DNA damage. We also found that WRNp foci partially co‐localize with sites of 5‐bromo‐2′‐deoxy‐uridine incorporation.ConclusionsThese findings suggest that WRNp form nuclear foci in response to aberrant DNA structures, including DNA double‐strand breaks and stalled replication forks. We propose that WRNp takes part in the homologous recombinational repair and in the processing of stalled replication forks.

Bibliography

Sakamoto, S., Nishikawa, K., Heo, S., Goto, M., Furuichi, Y., & Shimamoto, A. (2001). Werner helicase relocates into nuclear foci in response to DNA damaging agents and coâlocalizes with RPA and Rad51. Genes to Cells, 6(5), 421â430. Portico.

Authors 6

Shuichi Sakamoto (first)
Kaori Nishikawa (additional)
Seok‐Jin Heo (additional)
Makoto Goto (additional)
Yasuhiro Furuichi (additional)
Akira Shimamoto (additional)

References 48 Referenced 135

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Dates

Type	When
Created	22 years, 5 months ago (March 11, 2003, 5:47 p.m.)
Deposited	1 year, 9 months ago (Oct. 31, 2023, 12:11 p.m.)
Indexed	1 month, 2 weeks ago (July 11, 2025, 6:56 a.m.)
Issued	24 years, 3 months ago (May 1, 2001)
Published	24 years, 3 months ago (May 1, 2001)
Published Online	23 years, 8 months ago (Dec. 20, 2001)
Published Print	24 years, 3 months ago (May 1, 2001)

Funders 0

None

BibTeX

@article{Sakamoto_2001, title={Werner helicase relocates into nuclear foci in response to DNA damaging agents and co‐localizes with RPA and Rad51}, volume={6}, ISSN={1365-2443}, url={http://dx.doi.org/10.1046/j.1365-2443.2001.00433.x}, DOI={10.1046/j.1365-2443.2001.00433.x}, number={5}, journal={Genes to Cells}, publisher={Wiley}, author={Sakamoto, Shuichi and Nishikawa, Kaori and Heo, Seok‐Jin and Goto, Makoto and Furuichi, Yasuhiro and Shimamoto, Akira}, year={2001}, month=may, pages={421–430} }

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