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

2017 ◽  
Author(s):  
Niek van Wietmarschen ◽  
Sarra Merzouk ◽  
Nancy Halsema ◽  
Diana C.J. Spierings ◽  
Victor Guryev ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Genome Instability ◽  
Bloom Syndrome ◽  
Sister Chromatid Exchanges ◽  
Template Strand ◽  
Coding Regions ◽  
Guanine Quadruplex ◽  
Helicase Gene ◽  
Genomic Locations ◽  
Dna Template

AbstractBloom 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.

Single and twin sister chromatid exchanges in endoreduplicated Bloom Syndrome cells.

1982 ◽  
Vol 58 (8) ◽  
pp. 260-264 ◽  
Author(s):  
Yukimasa SHIRAISHI ◽  
Tosihide H. YOSIDA ◽  
Avery A. SANDBERG
Keyword(s):  
Sister Chromatid ◽  
Bloom Syndrome ◽  
Sister Chromatid Exchanges ◽  
Twin Sister ◽  
Chromatid Exchanges

scholarly journals Double-strand breaks are not the main cause of spontaneous sister chromatid exchange in wild-type yeast cells

2017 ◽  
Author(s):  
Clémence Claussin ◽  
David Porubský ◽  
Diana C.J. Spierings ◽  
Nancy Halsema ◽  
Stefan Rentas ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Sister Chromatid Exchange ◽  
Genome Instability ◽  
Single Cells ◽  
Double Strand Breaks ◽  
Yeast Cells ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Template Strand ◽  
Sister Chromatids

SummaryHomologous recombination involving sister chromatids is the most accurate, and thus most frequently used, form of recombination-mediated DNA repair. Despite its importance, sister chromatid recombination is not easily studied because it does not result in a change in DNA sequence, making recombination between sister chromatids difficult to detect. We have previously developed a novel DNA template strand sequencing technique, called Strand-seq, that can be used to map sister chromatid exchange (SCE) events genome-wide in single cells. An increase in the rate of SCE is an indicator of elevated recombination activity and of genome instability, which is a hallmark of cancer. In this study, we have adapted Strand-seq to detect SCE in the yeast Saccharomyces cerevisiae. Contrary to what is commonly thought, we find that most spontaneous SCE events are not due to the repair of DNA double-strand breaks.

scholarly journals The DNA Helicase Activity of BLM Is Necessary for the Correction of the Genomic Instability of Bloom Syndrome Cells

1999 ◽  
Vol 10 (3) ◽  
pp. 665-676 ◽  
Author(s):  
Norma F. Neff ◽  
Nathan A. Ellis ◽  
Tian Zhang Ye ◽  
James Noonan ◽  
Kelly Huang ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Nuclear Localization ◽  
Sister Chromatid ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Bloom Syndrome ◽  
Dna Helicase ◽  
Sister Chromatid Exchanges ◽  
Growth Deficiency ◽  
Chromatid Exchanges

Bloom syndrome (BS) is a rare autosomal recessive disorder characterized by growth deficiency, immunodeficiency, genomic instability, and the early development of cancers of many types. BLM, the protein encoded by BLM, the gene mutated in BS, is localized in nuclear foci and absent from BS cells. BLMencodes a DNA helicase, and proteins from three missense alleles lack displacement activity. BLM transfected into BS cells reduces the frequency of sister chromatid exchanges and restores BLM in the nucleus. Missense alleles fail to reduce the sister chromatid exchanges in transfected BS cells or restore the normal nuclear pattern. BLM complements a phenotype of aSaccharomyces cerevisiae sgs1 top3 strain, and the missense alleles do not. This work demonstrates the importance of the enzymatic activity of BLM for its function and nuclear localization pattern.

scholarly journals Genome-wide mapping of sister chromatid exchange events in single yeast cells using Strand-seq

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Clémence Claussin ◽  
David Porubský ◽  
Diana CJ Spierings ◽  
Nancy Halsema ◽  
Stefan Rentas ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Sister Chromatid Exchange ◽  
Genome Instability ◽  
Single Cells ◽  
Yeast Cells ◽  
Dna Double Strand Breaks ◽  
Yeast Saccharomyces Cerevisiae ◽  
Template Strand ◽  
Sister Chromatids ◽  
Genome Wide

Homologous recombination involving sister chromatids is the most accurate, and thus most frequently used, form of recombination-mediated DNA repair. Despite its importance, sister chromatid recombination is not easily studied because it does not result in a change in DNA sequence, making recombination between sister chromatids difficult to detect. We have previously developed a novel DNA template strand sequencing technique, called Strand-seq, that can be used to map sister chromatid exchange (SCE) events genome-wide in single cells. An increase in the rate of SCE is an indicator of elevated recombination activity and of genome instability, which is a hallmark of cancer. In this study, we have adapted Strand-seq to detect SCE in the yeast Saccharomyces cerevisiae. We provide the first quantifiable evidence that most spontaneous SCE events in wild-type cells are not due to the repair of DNA double-strand breaks.

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