Werner protein stimulates topoisomerase I DNA relaxation activity. - Archive ouverte HAL Access content directly
Journal Articles Cancer Research Year : 2003

Werner protein stimulates topoisomerase I DNA relaxation activity.

Abstract

Werner syndrome (WS) is a human premature aging disorder characterized by the early onset of age-related clinical features and an elevated incidence of cancer. The Werner protein (WRN) belongs to the RecQ family of DNA helicases and is required for the maintenance of genomic stability in human cells. Potential cooperation between RecQ helicases and topoisomerases in many aspects of DNA metabolism, such as the progression of replication forks, transcription, recombination, and repair, has been reported. Here, we show a physical and functional interaction between WRN and topoisomerase I (topo I). WRN colocalizes and interacts directly with topo I. WRN stimulates the ability of topo I to relax negatively supercoiled DNA and specifically stimulates the religation step of the relaxation reaction. Moreover, cell extracts from WS fibroblasts exhibit a decrease in the relaxation activity of negatively supercoiled DNA. We have identified two regions of WRN that mediate functional interaction with topo I, and they are located at the NH(2) and COOH termini of the WRN protein. In a reciprocal functional interaction, topo I inhibits the ATPase activity of WRN. Our data provide new insight into the interrelationship between RecQ helicases and topoisomerases in the maintenance of genomic integrity and prevention of tumorigenesis.
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Dates and versions

hal-04142667 , version 1 (27-06-2023)

Identifiers

  • HAL Id : hal-04142667 , version 1
  • PUBMED : 14612507

Cite

Jean-Philippe Laine, Patricia Opresko, Fred Indig, Jeanine Harrigan, Cayetano von Kobbe, et al.. Werner protein stimulates topoisomerase I DNA relaxation activity.. Cancer Research, 2003, 63 (21), pp.7136-46. ⟨hal-04142667⟩
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