WRN gene

The WRN gene (WRN stands for: Werner Syndrome RecQ Like Helicase) is a protein coding gene located on chromosome 8p12. The WRN gene encodes a member of the RecQ subfamily of DNA helicase proteins. The encoded nuclear protein is important for maintaining genome stability and plays a role in DNA repair, replication, transcription, and telomere maintenance. This protein contains an N-terminal 3'-5' exonuclease domain, an ATP-dependent helicase domain, and an RQC (RecQ helicase conserved region) domain in its central region, as well as a C-terminal HRDC (helicase RNase D C-terminal) domain and a nuclear localization signal.

WRN helicase is a multifunctional enzyme that has both magnesium- and ATP-dependent DNA helicase activity and 3'->5' exonuclease activity toward double-stranded DNA with a 5' overhang. Has no nuclease activity toward single-stranded DNA or blunt-ended double-stranded DNA. Helicase preferentially binds to DNA substrates containing alternative secondary structures, such as replication forks and Holliday junctions. It plays an important role in the dissociation of linked DNA molecules that may arise as products of homologous recombination, at stalled replication forks, or during DNA repair. Prevents DNA polymerase death at the site of DNA lesions and is important for genomic integrity. The enzyme plays a role in the formation of DNA replication foci; stably associates with foci that generate binding sites for RP-A; and plays a role in the repair of double-strand breaks after gamma irradiation.

Defects in this gene are the cause of Werner syndrome (progeria adultorum), an autosomal recessive progeria syndrome characterized by accelerated aging and increased risk of certain cancers. An important paralog of this gene is the BLM gene; mutations in this gene are associated with Bloom syndrome.

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