A study for genes interacting with the RecQ helicase

Abstract

Werner’s syndrome (WS) is an autosomal recessive disorder in humans characterized by the premature development of age-associated pathologies. WRN, the product of WRN gene which is defective in WS, plays a key role in protecting genome. The cell derived from WS patients show genomic instabilities such as telomere shortening. wrn- 1, a Caenorhabditis elegans (C. elegans) homolog of the WRN, was identified and its mutation also exhibited a shorter life span. Although many biochemical studies of WRN protein showed its role in DNA metabolism of DNA damage, the defect of WRN activity is not sufficient to explain several phenotypes of WS. Thus, other additional cellular deficits may better explain manifestations seen in WS. To study this unsolved question, we investigated the involvement of wrn-1 in organismal developments by the use of gene knockout in wrn-1 mutants. Our results showed that wrn-1 acts with either mre-11 or him-6 during oocyte and embryo developments. When the expression of both wrn-1 and mre-11 was reduced, larval development was greatly retarded compared with a single reduction of each gene in the N2 control worms. The reduced expression of him-6 in wrn-1 mutant resulted in increased embryonic lethality and arrested cell divisions in embryo. In addition, wrn-1(gk99);him-6(RNAi) or wrn-1(gk99);mre- 11(RNAi) worms displayed multiple chromosomal abnormalities in oocyte nuclei at the diakinesis stage. These results suggest that WRN-1 functionally interacts with MRE-11 or HIM-6 and its interaction is involved in organismal developments.