Exonuclease Domain
WRN contains an N-terminal domain with conserved residues that has been found in several other proteins with 3'-5' exonuclease activity. These proteins include the proofreading domain of E. coli DNA polymerase I, E. coli RNAseD and the 100-kDa human scleroderma autoantigen, PMSC. This nuclease domain is found only in WRN among the human RecQ helicases. A 3'-5' exonuclease activity has been identified in biochemical assays using WRN protein synthesized in insect cells.
RecQ Helicase Domain
A RecQ helicase domain occupies the central third of WRN. This helicase domain consists of seven short amino acid motifs found in many DNA and RNA helicases, including all members of the RecQ family. RecQ homologues have been identified in many bacterial genomes, in budding and fission yeast, in Caenorhabditis elegans, in Xenopus laevis, and in Mus musculus. Purified WRN protein possessess 3'-5' helicase activity, and can act on a range of substrates.
RQC domain
The RQC or RecQ consensus domain is shared across the RecQ helicase family. The RQC domain of WRN appears to act as a nucleolar localization signal, as well as an important site for the interaction of other proteins with WRN.
HRDC
The HRDC (Helicase, RNAseD C-terminal) domain, of unknown functional importance, is found near the C-terminus of both RecQ helicase and nuclease proteins from several species.This domain may play a role in substrate binding.
Nuclear Localization Signal The last 69 residues of WRN encodes a nuclear localization signal that can direct the localization of WRN-GFP fusion proteins to the nucleus of human cells.
References:
Additional information on WRN domains and functions can be found in the following three reviews: Moser MJ, Oshima J, Monnat RJ Jr. WRN mutations in Werner syndrome. Hum Mutat. 1999;13(4):271-9. Erratum in: Hum Mutat 1999;14(1):84-5. Shen JC, Loeb LA. The Werner syndrome gene: the molecular basis of RecQ helicase-deficiency diseases. Trends Genet. 2000 May;16(5):213-20. Hickson ID. RecQ helicases: caretakers of the genome. Nat Rev Cancer. 2003 Mar;3(3):169-78. Opresko PL, Cheng WH, Von Kobbe C, Harrigan JA, Bohr VA. Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process. Carcinogenesis. 2003 May;24(5):791-802.