BLM helicase suppresses recombination at G-quadruplex motifs in transcribed genes

Niek van Wietmarschen, Sarra Merzouk, Nancy Halsema, Diana C J Spierings, Victor Guryev, Peter M Lansdorp

Research output: Contribution to journalArticleAcademicpeer-review

31 Citations (Scopus)
311 Downloads (Pure)

Abstract

Bloom syndrome is a cancer predisposition disorder caused by mutations in the BLM helicase gene. Cells from persons with Bloom syndrome exhibit striking genomic instability characterized by excessive sister chromatid exchange events (SCEs). We applied single-cell DNA template strand sequencing (Strand-seq) to map the genomic locations of SCEs. Our results show that in the absence of BLM, SCEs in human and murine cells do not occur randomly throughout the genome but are strikingly enriched at coding regions, specifically at sites of guanine quadruplex (G4) motifs in transcribed genes. We propose that BLM protects against genome instability by suppressing recombination at sites of G4 structures, particularly in transcribed regions of the genome.

Original languageEnglish
Article number271
Number of pages12
JournalNature Communications
Volume9
Issue number1
Early online date18-Jan-2018
DOIs
Publication statusPublished - 18-Jan-2018

Keywords

  • SISTER-CHROMATID EXCHANGE
  • BLOOM-SYNDROME CELLS
  • DOUBLE-STRAND BREAK
  • REPLICATION-FORK
  • TOPOISOMERASE-I
  • RECQ HELICASES
  • FRAGILE SITES
  • HUMAN GENOME
  • DNA
  • HETEROZYGOSITY

Cite this