PT  - JOURNAL ARTICLE
AU  - Niek van Wietmarschen
AU  - Sarra Merzouk
AU  - Nancy Halsema
AU  - Diana C.J. Spierings
AU  - Victor Guryev
AU  - Peter M. Lansdorp
TI  - BLM helicase suppresses recombination at G-quadruplex motifs in transcribed genes
AID  - 10.1101/173252
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 173252
4099  - http://biorxiv.org/content/early/2017/08/07/173252.short
4100  - http://biorxiv.org/content/early/2017/08/07/173252.full
AB  - 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 at a resolution that is orders of magnitude better than was previously possible. Our results show that, in the absence of BLM, sister chromatid exchanges in human and murine cells do not occur randomly throughout the genome but are strikingly enriched at coding regions, specifically at sites of putative 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.