Roles of Caenorhabditis elegans WRN Helicase in DNA Damage Responses, and a Comparison with Its Mammalian Homolog: A Mini-Review.
Werner syndrome protein (WRN) is unusual among RecQ family DNA helicases in having an additional exonuclease activity. WRN is involved in the repair of double-strand DNA breaks via the homologous recombination and nonhomologous end joining pathways, and also in the base excision repair pathway. In addition, the protein promotes the recovery of stalled replication forks. The helicase activity is thought to unwind DNA duplexes, thereby moving replication forks or Holliday junctions. The targets of the exonuclease could be the nascent DNA strands at a replication fork or the ends of double-strand DNA breaks. However, it is not clear which enzyme activities are essential for repairing different types of DNA damage. Model organisms such as mice, flies, and worms deficient in WRN homologs have been investigated to understand the physiological results of defects in WRN activity. Premature aging, the most remarkable characteristic of Werner syndrome, is also seen in the mutant mice and worms, and hypersensitivity to DNA damage has been observed in WRN mutants of all three model organisms, pointing to conservation of the functions of WRN. In the nematode Caenorhabditis elegans, the WRN homolog contains a helicase domain but no exonuclease domain, so that this animal is very useful for studying the in vivo functions of the helicase without interference from the activity of the exonuclease. Here, we review the current status of investigations of C. elegans WRN-1 and discuss its functional differences from the mammalian homologs.
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
Jin-Sun
JS
Ryu
Hyeon-Sook
HS
Koo
D019588:Aging, Premature / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics* / Q000502:physiology; D004260:DNA Repair; D006801:Humans; D051379:Mice; D000071657:Werner Syndrome Helicase
D029742:Caenorhabditis elegans Proteins; D004265:DNA Helicases; D000071657:Werner Syndrome Helicase; C488009:WRN-1 protein, C elegans