Synthetic Lethal Interactions of RECQ Helicases

Trends Cancer. 2021 Feb;7(2):146-161. doi: 10.1016/j.trecan.2020.09.001. Epub 2020 Oct 9.

Abstract

DNA helicases have risen to the forefront as genome caretakers. Their prominent roles in chromosomal stability are demonstrated by the linkage of mutations in helicase genes to hereditary disorders with defects in DNA repair, the replication stress response, and/or transcriptional activation. Conversely, accumulating evidence suggests that DNA helicases in cancer cells have a network of pathway interactions such that codeficiency of some helicases and their genetically interacting proteins results in synthetic lethality (SL). Such genetic interactions may potentially be exploited for cancer therapies. We discuss the roles of RECQ DNA helicases in cancer, emphasizing some of the more recent developments in SL.

Keywords: Bloom’s syndrome; RECQ; Rothmund–Thomson Syndrome; Werner syndrome; cancer; genetic disease; genomic stability; helicase; synthetic lethality.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • DNA Repair / drug effects
  • DNA Replication / drug effects
  • Gene Knockdown Techniques
  • Genomic Instability / drug effects
  • Humans
  • Medical Oncology / methods
  • Medical Oncology / trends
  • Mice
  • Mutation
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Precision Medicine / methods
  • Precision Medicine / trends
  • RecQ Helicases / antagonists & inhibitors
  • RecQ Helicases / genetics
  • RecQ Helicases / metabolism*
  • Synthetic Lethal Mutations / drug effects*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • RecQ Helicases