A5006862779- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Cancer therapeutics and mechanisms
- DNA and Nucleic Acid Chemistry
- CRISPR and Genetic Engineering
- Microtubule and mitosis dynamics
- Carcinogens and Genotoxicity Assessment
- Chromosomal and Genetic Variations
- Fungal and yeast genetics research
- Polyomavirus and related diseases
- Bacterial Genetics and Biotechnology
- Mitochondrial Function and Pathology
- Acute Lymphoblastic Leukemia research
- Antibiotic Resistance in Bacteria
- Yeasts and Rust Fungi Studies
- Genetic factors in colorectal cancer
- Epigenetics and DNA Methylation
- Genetic diversity and population structure
- Plant Reproductive Biology
- Telomeres, Telomerase, and Senescence
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Drug Transport and Resistance Mechanisms
- Phenothiazines and Benzothiazines Synthesis and Activities
- Metabolism and Genetic Disorders
- Gene expression and cancer classification
University of Sussex
2013-2024
Memorial Sloan Kettering Cancer Center
2005-2011
University of Sheffield
2002-2010
Howard Hughes Medical Institute
2009
During meiotic prophase, chromosomes organise into a series of chromatin loops emanating from proteinaceous axis, but the mechanisms assembly remain unclear. Here we use Saccharomyces cerevisiae to explore how this elaborate three-dimensional chromosome organisation is linked genomic sequence. As cells enter meiosis, observe that strong cohesin-dependent grid-like Hi-C interaction patterns emerge, reminiscent mammalian interphase organisation, with distinct regulation. Meiotic agree...
Abstract DNA topoisomerases are required to resolve topological stress. Despite this essential role, abortive topoisomerase activity generates aberrant protein-linked breaks, jeopardising genome stability. Here, understand the genomic distribution and mechanisms underpinning topoisomerase-induced we map Top2 cleavage with strand-specific nucleotide resolution across S . cerevisiae human genomes—and use meiotic Spo11 protein validate broad applicability of method explore role diverse family...
Abstract The meiotic chromosome axis coordinates organization and interhomolog recombination in prophase is essential for fertility. In S. cerevisiae , the HORMAD protein Hop1 mediates enrichment of proteins at nucleosome-rich islands through a central chromatin-binding region (CBR). Here, we use cryoelectron microscopy to show that CBR directly recognizes bent nucleosomal DNA composite interface its PHD winged helix–turn–helix domains. Targeted disruption CBR-nucleosome causes localized...
DNA end resection plays a critical function in double-strand break repair pathway choice. Resected ends are refractory to end-joining mechanisms and instead channeled homology-directed repair. Using biochemical, genetic, imaging methods, we show that phosphorylation of Saccharomyces cerevisiae Sae2 controls its capacity promote the Mre11-Rad50-Xrs2 (MRX) nuclease initiate blocked by at least two distinct mechanisms. First, damage cell cycle-dependent leads tetramerization. Second,...
During meiosis, formation and repair of programmed DNA double-strand breaks (DSBs) create genetic exchange between homologous chromosomes—a process that is critical for reductional meiotic chromosome segregation the production genetically diverse sexually reproducing populations. Meiotic DSB a complex process, requiring numerous proteins, which Spo11 evolutionarily conserved catalytic subunit. Precisely how its accessory proteins function or are regulated unclear. Here, we use Saccharomyces...
During meiosis, genetic recombination is initiated by the formation of many DNA double-strand breaks (DSBs) catalysed evolutionarily conserved topoisomerase-like enzyme, Spo11, in preferred genomic sites known as hotspots. DSB activates Tel1/ATM damage responsive (DDR) kinase, locally inhibiting Spo11 activity adjacent hotspots via a process interference. Intriguingly, S . cerevisiae , over short distances (<15 kb), displays characteristics concerted or clustering, wherein frequency...
Meiotic recombination shows broad variations across species and along chromosomes is often suppressed at around genomic regions determining sexual compatibility such as mating type loci in fungi. Here, we show that the absence of Spo11-DSBs meiotic on Lakl0C-left, chromosome arm containing sex locus Lachancea kluyveri budding yeast, results from recruitment two axis proteins Red1 Hop1, essential for proper formation. Furthermore, cytological observation spread pachytene reveals Lakl0C-left...
Abstract DNA replication and transcription generate supercoiling, which can cause topological stress intertwining of daughter chromatin fibers, posing challenges to the completion chromosome segregation. Type II topoisomerases (Top2s) are enzymes that relieve supercoiling decatenate braided sister chromatids. How Top2 complexes deal with in different contexts, whether all chromosomal contexts subjected equally torsional require activity is unknown. Here we show catalytic inhibition complex...