Адам геномының WRN гені және Вернер синдромы

Protein coding gene in the species Homo sapiens

Werner syndrome ATP dependent helicase, also known as DNA helicase, RecQ like type 3, is an enzyme that in humans is encoded by the WRN gene. WRN is a member of the RecQ Helicase family. or non homologous end joining, repair of single nucleotide damages by base excision repair, and is effective in replication arrest recovery. WRN may also be important in telomere maintenance and replication, especially the replication of the G rich sequences. WRN is an oligomer that can act as a monomer when unwinding DNA, but as a dimer in solution or a tetramer when complexed with DNA, and has also been observed in hexameric forms. The diffusion of WRN has been measured to 1.62 in nucleoplasm and 0.12 at nucleoli. Orthologs of WRN have been found in a number of other organisms, including Drosophila, Xenopus, and C. elegans. WRN is important to genome stability, and cells with mutations to WRN are more susceptible to DNA damage and DNA breaks. The amino terminus of WRN is involved in both helicase and nuclease activities, while the carboxyl terminus interacts with p53, an important tumor suppressor.

Phosphorylation of WRN at serine/threonine inhibits helicase and exonuclease activities which are important to post replication DNA repair. De phosphorylation at these sites enhances the catalytic activities of WRN. Phosphorylation may affect other post translational modifications, including sumoylation and acetylation.

Werner syndrome is caused by mutations in the WRN gene. This shortened protein may also be broken down too quickly, leading to a loss of Werner protein in the cell. Without normal Werner protein in the nucleus, cells cannot perform the tasks of DNA replication, repair, and transcription. Researchers are still determining how these mutations cause the appearance of premature aging seen in Werner syndrome.

WRN is active in homologous recombination. Cells defective in the WRN gene have a 23 fold reduction in spontaneous mitotic recombination, with especial deficiency in conversion type events. WRN defective cells, when exposed to x rays, have more chromosome breaks and micronuclei than cells with wild type WRN. Cells defective in the WRN gene are not more sensitive than wild type cells to gamma irradiation, UV light, 4 – 6 cyclobutane pyrimidines, or mitomycin C, but are sensitive to type I and type II topoisomerase inhibitors. These findings suggested that the WRN protein takes part in homologous recombinational repair and in the processing of stalled replication forks.