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3.6.4.12 RecQ helicases family

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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RecQ helicases use the energy from ATP hydrolysis to unwind DNA and/or RNA. There are 5 genes for RecQ helicases in the human genome: BLM, WRN, RECQ1, RECQ4, and RECQ5. The RecQ helicases play important roles in maintaining genome integrity during replication [22], participate in DNA repair pathways (especially homologous recombination) [6], and are involved in facilitating tolerance of microsatellite instability (e.g. in cancer cells) [3-4,10]. Defects in the genes for some of these enzymes have been linked with rare genetic diseases that are characterised by genomic instability and cancer predisposition. In cancers that carry genetic alterations that give rise to microsatellite instability and/or DNA repair defects inhibitors of BLM and WRN helicase functions are proposed as novel cancer therapeutic options that exploit the mechanism of synthetic lethality.

Enzymes

3259
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BLM RecQ like helicase Show summary »

WRN RecQ like helicase Show summary »


Target Id 3259
Nomenclature WRN RecQ like helicase
Previous and unofficial names Werner helicase | Werner syndrome protein | Werner syndrome ATP-dependent helicase
Genes WRN (Hs), Wrn (Mm), Wrn (Rn)
Ensembl ID ENSG00000165392 (Hs), ENSMUSG00000031583 (Mm), ENSRNOG00000015440 (Rn)
UniProtKB AC Q14191 (Hs), O09053 (Mm)
EC number
3.6.4.12
Inhibitors
H3B-960 pKi 7.5 [15]
H3B-968 pIC50 8.0 [15]
H3B-960 pIC50 7.7 [15]
VVD-133214 pIC50 7.0 [1] - Mouse
HRO761 pIC50 7.0 [2]
VVD-133214 pIC50 6.9 [1]
ML216 pIC50 5.6 [19]
compound 6 [PMID: 38134034] pIC50 4.9 [17]
Comment The WRN gene encodes an enzyme with helicase and 3'-5' exonuclease activities [11]. The enzyme's functions support DNA replication, repair, recombination, transcription, and chromosome stability, with a role in telomere stability [18]. Mutations in WRN which result in WRN deficiency are known to cause Werner syndrome (a premature aging disorder) [20]. WRN has been identified as an actionable molecular target for the development of anti-tumour agents, based on the observation that WRN inactivation is synthetically lethal in cancer cells with microsatellite instability [3,8,13-14,16,23,25]. A WRN inhibitor has entered clinical study to determine efficacy in tumours with microsatellite instability or mismatch repair deficits, which makes them more vulnerable to inhibition of compensatory DNA repair mechanisms such as WRN.

References

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How to cite this family page

Database page citation:

3.6.4.12 RecQ helicases family. Accessed on 07/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1091.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Enzymes. Br J Pharmacol. 180 Suppl 2:S289-373.