DNA helicases are involved in many aspects of DNA metabolism, including transcription, replication, recombination, and repair. One of the most important functions of DNA helicases is the unwinding of DNA during DNA replication as a component in a replication complex. Another function of helicase involves DNA repair. It has been hypothesized that some forms of nucleotide excision repair are coupled with transcription; mutant helicases responsible for the DNA instability syndromes may impair lesion recognition and/or lesion removal of the damaged nucleotides during transcription.

The RECQL2 protein contains a nuclear localization signal in the C-terminus and shows a predominant nucleolar localization. It possesses an intrinsic 3' to 5' DNA helicase activity, and is also a 3' to 5' exonuclease.

Mutations in the RECQ Protein-Like 2 (RECQL2 gene, also known as WRN gene) causes Werner syndrome. The RECQL2 gene is a member of the RecQ family of DNA helicases. It contains 35 exons, each 68 to 767 bp, with the coding sequence beginning in the second exon. The RECQL2 gene encodes a 1,432 amino acid protein partially homologous to RecQ helicases. The region most highly homologous to RecQ-type helicases is located in exons 14 through 21.

Disease-linked mutations are found throughout the RECQL2 gene and include stop codons, splice site variants, and insertions/deletions that generate frameshift mutations. Missense mutations in RECQL2 have not been detected in Werner syndrome patients. All identified RECQL2 mutations predict the synthesis of truncated protein products lacking the C-terminal nuclear localization signal. Based on this observation, it has been proposed that the lack of a nuclear localization signal is important in the pathogenesis of Werner syndrome.