Genome-wide investigations on regulatory functions of RECQ1 helicase

Methods. 2022 Aug:204:263-268. doi: 10.1016/j.ymeth.2022.02.010. Epub 2022 Feb 26.

Abstract

DNA helicase RECQ1 (also known as RECQL or RECQL1) is a candidate breast cancer susceptibility gene significantly correlated with clinical outcomes of sporadic breast cancer patients. Prior studies have suggested that RECQ1 maintains genomic stability by regulating a wide variety of core cellular functions including DNA replication, DNA damage response, and transcription. However, it is unclear which, if any, of these are the primary functions of RECQ1 as related to its role in suppressing breast cancer. We describe here an unbiased integrative genomics approach that enabled us to discover a previously unknown regulatory role of RECQ1 in promoting Estrogen Receptor alpha (ERα) expression and the expression of specific ERα target genes in ER positive breast cancer cells. We discuss potential future applications of similar experimental strategies in advancing the mechanistic understanding and elucidating specific new details of genome-wide functions of RECQ1 and other RecQ helicases in maintaining genomic stability and preventing cancer.

Keywords: ChIP-seq; DNA helicase; Estrogen receptor; FOXA1; G4; R-loops; RECQ1; RNA-DNA hybrid; Transcriptional regulation.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Breast Neoplasms* / genetics
  • Estrogen Receptor alpha / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genomic Instability
  • Humans
  • RecQ Helicases* / genetics

Substances

  • Estrogen Receptor alpha
  • RECQL protein, human
  • RecQ Helicases