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


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.

SUBMITTER: van Wietmarschen N 

PROVIDER: S-EPMC5773480 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

van Wietmarschen Niek N   Merzouk Sarra S   Halsema Nancy N   Spierings Diana C J DCJ   Guryev Victor V   Lansdorp Peter M PM  

Nature communications 20180118 1


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 cod  ...[more]

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