A5076547216- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Prenatal Screening and Diagnostics
- Fungal and yeast genetics research
- Epigenetics and DNA Methylation
- Plant Molecular Biology Research
- Photosynthetic Processes and Mechanisms
- Mitochondrial Function and Pathology
- Reproductive Biology and Fertility
- Chromosomal and Genetic Variations
- Evolution and Genetic Dynamics
- Genetic Neurodegenerative Diseases
- Bacteriophages and microbial interactions
- Monoclonal and Polyclonal Antibodies Research
- Gene expression and cancer classification
- Advanced Biosensing Techniques and Applications
Indian Institute of Science Education and Research, Tirupati
2022-2025
New York University
2011-2019
Dartmouth College
2008-2009
Faithful meiotic chromosome segregation and fertility require recombination between homologous chromosomes rather than the equally available sister chromatid, a bias that in Saccharomyces cerevisiae depends on kinase, Mek1. Mek1 is thought to mediate repair template by specifically suppressing sister-directed repair. Instead, we found when persists closely paired (synapsed) homologues, DNA severely delayed, suggesting suppresses any proximal template. Accordingly, excluded from synapsed...
Abstract Faithful meiotic chromosome inheritance and fertility rely on the stimulation of crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs, likely in response to initiation repair. In Saccharomyces cerevisiae , this regulation requires removal conserved DSB-promoting protein Hop1/HORMAD during synapsis. Here, we identify privileged end-adjacent regions (EARs) spanning roughly 100 kb near all...
In humans, meiotic chromosome segregation errors increase dramatically as women age, but the molecular defects responsible are largely unknown. Cohesion along arms of sister chromatids provides an evolutionarily conserved mechanism to keep recombinant chromosomes associated until anaphase I. One attractive hypothesis explain age-dependent nondisjunction (NDJ) is that loss cohesion over time causes homologues dissociate prematurely and segregate randomly during first division. Using...
Accurate chromosome segregation during meiosis relies on the presence of crossover events distributed among all chromosomes. MutSγ and MutLγ homologs (Msh4/5 Mlh1/3) facilitate formation a prominent group meiotic crossovers that mature within context an elaborate chromosomal structure called synaptonemal complex (SC). SC proteins are required for intermediate steps in MutSγ-MutLγ crossovers, but whether assembled per se is MutSγ-MutLγ-dependent recombination unknown. Here we describe...
Abstract In many organisms, meiotic crossover recombination is suppressed near the extreme ends of chromosomes. Here, we identified two chromatin modifiers, histone methyltransferase Dot1 and Sir silencing complex, as regulators this process in Saccharomyces cerevisiae . We show that recombination-promoting axis proteins Red1 Hop1, but not axis-associated cohesin Rec8, are significantly reduced within 20 kb telomeres compared to chromosome interior. Dot1, which preferentially methylates...
Normally, meiotic crossovers in conjunction with sister-chromatid cohesion establish a physical connection between homologs that is required for their accurate segregation during the first division. However, some organisms an alternative mechanism ensures proper of bivalents fail to recombine. In Drosophila oocytes, achiasmate depends on pairing mediated by centromere-proximal heterochromatin. Our previous work uncovered unexpected link and fidelity when oocytes are experimentally aged. Here...
SUMMARY Faithful meiotic chromosome inheritance and fertility relies on the stimulation of crossover recombination by potentially genotoxic DNA double-strand breaks (DSBs). To avoid excessive damage, feedback mechanisms down-regulate DSBs chromosomes that have successfully initiated repair. In Saccharomyces cerevisiae , this regulation requires removal conserved DSB-promoting protein Hop1/HORMAD during synapsis. Here, we identify privileged end-adjacent regions (EARs) spanning roughly 100 Kb...
Abstract Programmed double strand DNA breaks in meiosis can be repaired as inter-homologue crossovers and thereby aid the faithful segregation of homologous chromosomes. Biased repair mechanisms enforce with homologue. Further, left unrepaired lead to checkpoint activation. Meiosis-specific Chk2 kinase budding yeast mediates biased meiotic DSBs using homologue partner but also enforces checkpoint. Here we investigate Mek1 activity by analyzing novel point mutants derived from an EMS...
Age-dependent loss of cohesion is a determinant aneuploidy in human oocytes. Mechanisms for how this triggered with age are not known. Using oocytes from participants various ages, the authors correlate Sgo2, protector cohesins, age-related meiosis II defects including increased inter-kinetochore distances and single chromatids. High-resolution microscopy reveals age-dependent Sgo2 specifically pericentromeric bridges, but centromeric regions. This study highlights role cohesins upholding...
Cohesins organize chromatin within the nucleus by promoting loop extrusion via cis contacts on and sister chromatid cohesion trans between chromatids. Whether cohesins employ a distinct mechanism for these two functions is not known. The authors use carefully designed conditional expression of cohesin, mutated at its hinge domain, assess function with variety in vitro vivo experiments including live TIRF imaging, assay, Hi-C, calibrated ChIP sequencing. A mutation domain separates as mutant...
Cohesins play an important role in organizing the meiotic chromosome structure, but how cohesins themselves are regulated during this process is not entirely clear. Taking advantage of conditional depletion, point mutations and quantitative immunofluorescence, study finds that kinase CHK‐2 a master regulator cohesin stabilization meiosis Caenorhabditis elegans. Surprisingly, CHK‐2, known downstream effector ATM‐1 DNA damage response, promotes activity worm germline. Curiously, consensus...
Many commonly used protein epitope tags are optimized for one or a few biological applications. The recently developed ALFA tag performs well across broad range of cell applications including localization, biochemical, and functional studies but has not been available in budding yeast. This study engineers modular plasmid-based platform to introduce on proteins interest yeast detection via fluorescently tagged nanobodies. toolkit offers excellent performance quantitative live imaging,...