Michael Lichten

Bio: Michael Lichten is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Homologous recombination & Meiosis. The author has an hindex of 41, co-authored 73 publications receiving 7504 citations. Previous affiliations of Michael Lichten include Brandeis University & Massachusetts Institute of Technology.

Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae

Abstract: In the yeast Saccharomyces cerevisiae, meiotic recombination is initiated by double-strand DNA breaks (DSBs). Meiotic DSBs occur at relatively high frequencies in some genomic regions (hotspots) and relatively low frequencies in others (coldspots). We used DNA microarrays to estimate variation in the level of nearby meiotic DSBs for all 6,200 yeast genes. Hotspots were nonrandomly associated with regions of high G + C base composition and certain transcriptional profiles. Coldspots were nonrandomly associated with the centromeres and telomeres.

Meiosis-induced double-strand break sites determined by yeast chromatin structure.

Abstract: Double-strand DNA breaks (DSBs) occur at recombination hotspots during Saccharomyces cerevisiae meiosis and are thought to initiate exchange at these loci. Analysis of DSB sites in three regions of the yeast genome indicated that breaks occur at or near many potential transcription promoters and that DSBs initiate most, if not all, meiotic recombination. DSB sites displayed deoxyribonuclease I hypersensitivity in chromatin from mitotic and meiotic cells, and changes in chromatin structure produced parallel changes in the occurrence of DSBs. Thus, features of chromatin structure that are established before meiosis play a role in determining where meiotic recombination events initiate.

Initial sequencing and analysis of the human genome.

Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

A haplotype map of the human genome

Abstract: Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution.

Capturing Chromosome Conformation

Abstract: We describe an approach to detect the frequency of interaction between any two genomic loci. Generation of a matrix of interaction frequencies between sites on the same or different chromosomes reveals their relative spatial disposition and provides information about the physical properties of the chromatin fiber. This methodology can be applied to the spatial organization of entire genomes in organisms from bacteria to human. Using the yeast Saccharomyces cerevisiae, we could confirm known qualitative features of chromosome organization within the nucleus and dynamic changes in that organization during meiosis. We also analyzed yeast chromosome III at the G1 stage of the cell cycle. We found that chromatin is highly flexible throughout. Furthermore, functionally distinct AT- and GC-rich domains were found to exhibit different conformations, and a population-average 3D model of chromosome III could be determined. Chromosome III emerges as a contorted ring.

Multiple Pathways of Recombination Induced by Double-Strand Breaks in Saccharomyces cerevisiae

Abstract: The budding yeast Saccharomyces cerevisiae has been the principal organism used in experiments to examine genetic recombination in eukaryotes. Studies over the past decade have shown that meiotic recombination and probably most mitotic recombination arise from the repair of double-strand breaks (DSBs). There are multiple pathways by which such DSBs can be repaired, including several homologous recombination pathways and still other nonhomologous mechanisms. Our understanding has also been greatly enriched by the characterization of many proteins involved in recombination and by insights that link aspects of DNA repair to chromosome replication. New molecular models of DSB-induced gene conversion are presented. This review encompasses these different aspects of DSB-induced recombination in Saccharomyces and attempts to relate genetic, molecular biological, and biochemical studies of the processes of DNA repair and recombination.