K. T. Nishant

Learn More
Accurate estimates of mutation rates provide critical information to analyze genome evolution and organism fitness. We used whole-genome DNA sequencing, pulse-field gel electrophoresis, and comparative genome hybridization to determine mutation rates in diploid vegetative and meiotic mutation accumulation lines of Saccharomyces cerevisiae. The vegetative(More)
During meiosis, the Msh4-Msh5 complex is thought to stabilize single-end invasion intermediates that form during early stages of recombination and subsequently bind to Holliday junctions to facilitate crossover formation. To analyze Msh4-Msh5 function, we mutagenized 57 residues in Saccharomyces cerevisiae Msh4 and Msh5 that are either conserved across all(More)
Interference-dependent crossing over in yeast and mammalian meioses involves the mismatch repair protein homologs MSH4-MSH5 and MLH1-MLH3. The MLH3 protein contains a highly conserved metal-binding motif DQHA(X)(2)E(X)(4)E that is found in a subset of MLH proteins predicted to have endonuclease activities (Kadyrov et al. 2006). Mutations within this motif(More)
Meiotic recombination occurs preferentially at certain regions called hot spots and is important for generating genetic diversity and proper segregation of chromosomes during meiosis. Hot spots have been characterized most extensively in yeast, mice and humans. The development of methods based on sperm typing and population genetics has facilitated rapid(More)
Crossing over between homologous chromosomes occurs during the prophase of meiosis I and is critical for chromosome segregation. In baker's yeast, two heterodimeric complexes, Msh4-Msh5 and Mlh1-Mlh3, act in meiosis to promote interference-dependent crossing over. Mlh1-Mlh3 also plays a role in DNA mismatch repair (MMR) by interacting with Msh2-Msh3 to(More)
High-throughput DNA analyses are increasingly being used to detect rare mutations in moderately sized genomes. These methods have yielded genome mutation rates that are markedly higher than those obtained using pre-genomic strategies. Recent work in a variety of organisms has shown that mutation rate is strongly affected by sequence context and genome(More)
Evolutionary theory assumes that mutations occur randomly in the genome; however, studies performed in a variety of organisms indicate the existence of context-dependent mutation biases. Sources of mutagenesis variation across large genomic contexts (e.g., hundreds of bases) have not been identified. Here, we use high-coverage whole-genome sequencing of a(More)
The Msh4-Msh5 protein complex in eukaryotes is involved in stabilizing Holliday junctions and its progenitors to facilitate crossing over during Meiosis I. These functions of the Msh4-Msh5 complex are essential for proper chromosomal segregation during the first meiotic division. The Msh4/5 proteins are homologous to the bacterial mismatch repair protein(More)
Our current knowledge of recombination hot spot activity in mammalian systems implicates a role for both the primary DNA sequence and the nature of the chromatin domain around it. In mice, the only recombination hot spots mapped to date have been confined to a cluster within the major histocompatibility complex (MHC) region. We present a high resolution(More)
The segregation of homologous chromosomes during the Meiosis I division requires an obligate crossover per homolog pair (crossover assurance). In Saccharomyces cerevisiae and mammals, Msh4 and Msh5 proteins stabilize Holliday junctions and its progenitors to facilitate crossing over. S. cerevisiae msh4/5 hypomorphs that reduce crossover levels up to twofold(More)