A5106695774- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Gene expression and cancer classification
- DNA and Nucleic Acid Chemistry
- Pluripotent Stem Cells Research
- Genomic variations and chromosomal abnormalities
- RNA Research and Splicing
- Renal and related cancers
- Cancer Genomics and Diagnostics
- Advanced biosensing and bioanalysis techniques
- BRCA gene mutations in cancer
- Single-cell and spatial transcriptomics
- RNA modifications and cancer
- PARP inhibition in cancer therapy
- Genetic factors in colorectal cancer
- RNA Interference and Gene Delivery
- Microtubule and mitosis dynamics
- Metalloenzymes and iron-sulfur proteins
- Genetic Neurodegenerative Diseases
- Cancer-related Molecular Pathways
- Biochemical and Molecular Research
- Genetic Syndromes and Imprinting
- Plant Disease Resistance and Genetics
- RNA and protein synthesis mechanisms
National Cancer Institute
2018-2022
National Human Genome Research Institute
2018-2022
Government of the United States of America
2021
University of Groningen
2012-2019
University Medical Center Groningen
2012-2018
Bloom syndrome is a cancer predisposition disorder caused by mutations in the BLM helicase gene. Cells from persons with exhibit striking genomic instability characterized excessive sister chromatid exchange events (SCEs). We applied single-cell DNA template strand sequencing (Strand-seq) to map locations of SCEs. Our results show that absence BLM, SCEs human and murine cells do not occur randomly throughout genome but are strikingly enriched at coding regions, specifically sites guanine...
Haplotypes are fundamental to fully characterize the diploid genome of an individual, yet methods directly chart unique genetic makeup each parental chromosome lacking. Here we introduce single-cell DNA template strand sequencing (Strand-seq) as a novel approach phasing genomes along entire length all chromosomes. We demonstrate this by building complete haplotype for HapMap individual (NA12878) at high accuracy (concordance 99.3%), without using generational information or statistical...
Sister chromatid exchanges (SCEs) are considered sensitive indicators of genome instability. Detection SCEs typically requires cells to incorporate bromodeoxyuridine (BrdU) during two rounds DNA synthesis. Previous studies have suggested that induced by replication over BrdU-substituted and BrdU incorporation alone could be responsible for the high number SCE events observed in from patients with Bloom syndrome (BS), a rare genetic disorder characterized marked instability frequency. Here we...
The maintenance of genome stability relies on coordinated control origin activation and replication fork progression. How the interplay between these processes influences human genetic disease cancer remains incompletely characterized. Here we show that mouse cells featuring Polε instability exhibit impaired genome-wide DNA origins, in an origin-location-independent manner. Strikingly, Trp53 ablation primary hypomorphic increased levels reduced damage a transcription-dependent Transcriptome...
Summary Genomic double-stranded DNA (dsDNA) becomes single-stranded (ssDNA) during replication, transcription, and repair. ssDNA is therefore believed to be transient, occurring in only a fraction of the genome at given time, variable amongst population cells. These transiently formed segments can also adopt alternative, dynamic conformations, such as cruciform DNA, triplexes, quadruplexes others. To determine whether there are stable conserved regions ssDNA, we utilized our previously...
Abstract Bloom syndrome is a cancer predisposition disorder caused by mutations in the BLM helicase gene. Cells from persons with exhibit striking genomic instability characterized excessive sister chromatid exchange events (SCEs). We applied single-cell DNA template strand-sequencing (Strand-seq) to map locations of SCEs at resolution that orders magnitude better than was previously possible. Our results show that, absence BLM, exchanges human and murine cells do not occur randomly...
The maintenance of genome stability relies on the coordinated control origin activation and replication fork progression. How interplay between these processes impacts human genetic disease cancer remains incompletely characterized. Here we show that mouse cells lacking Pole4 featuring Polε instability exhibit impaired genome-wide DNA origins. Lack POLE4 leads to proteasome-dependent Pole degradation prior CMG (CDC45/MCM2-7/GINS) helicase formation activation. Strikingly, Trp53 ablation in...