A5071778345- DNA Repair Mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Photosynthetic Processes and Mechanisms
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- Reproductive Biology and Fertility
- Nuclear Structure and Function
- Spaceflight effects on biology
- Ubiquitin and proteasome pathways
- Chromatin Remodeling and Cancer
- Insect and Arachnid Ecology and Behavior
- Fungal and yeast genetics research
- Plant and animal studies
- Cancer Mechanisms and Therapy
- Muscle Physiology and Disorders
- Genetic Neurodegenerative Diseases
- Semiconductor materials and interfaces
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Semiconductor materials and devices
- Plant Reproductive Biology
- Molecular Junctions and Nanostructures
- MicroRNA in disease regulation
University of Iowa
2014-2025
Tel Aviv University
1997
Repair of double-strand DNA breaks (DSBs) by the homologous recombination (HR) pathway results in crossovers (COs) required for a successful first meiotic division. Mre11 is one member MRX/N (Mre11, Rad50, and Xrs2/Nbs1) complex DSB formation resection Saccharomyces cerevisiae. In Caenorhabditis elegans, evidence role limited. We report separation-of-function allele, mre-11(iow1) C. which specifically defective but not formation. The mutants displayed chromosomal fragmentation aggregation...
During meiosis, evolutionarily conserved mechanisms regulate chromosome remodeling, leading to the formation of a tight bivalent structure. This bivalent, linked pair homologous chromosomes, is essential for proper segregation in meiosis. The involves condensation and restructuring around crossover. synaptonemal complex (SC), which mediates association before crossover formation, disassembles concurrently with increased during remodeling. Both SC disassembly are likely critical steps...
Studies of the repair pathways associated with DNA double strand breaks (DSBs) are numerous, and provide evidence for cell-cycle specific regulation homologous recombination (HR) by its proteins. Laser microirradiation is a well-established method to examine in vitro kinetics allows live-imaging DSB from moment induction. Here we apply this whole, live organisms, introducing an effective system analyze exogenous, microirradiation-induced Caenorhabditis elegans germline. Through observed...
The synaptonemal complex (SC) is a conserved protein structure that holds homologous chromosome pairs together throughout much of meiotic prophase I. It essential for the formation crossovers, which are required proper segregation chromosomes into gametes. assembly SC likely to be regulated by post-translational modifications. CSN/COP9 signalosome has been shown act in many pathways, mainly via ubiquitin degradation/proteasome pathway. Here we examine role model organism C. elegans. Our work...
Faithful meiotic segregation requires pairwise alignment of the homologous chromosomes and their synaptonemal complex (SC) mediated stabilization. Here, we investigate factors that promote coordinate these events during C. elegans meiosis. We identify BRA-2 (BMP Receptor Associated family member 2) as an interactor HIM-17, previously shown to double-strand break formation. found loss bra-2 impairs synapsis elongation without affecting homolog recognition, chromosome movement or SC...
Abstract DNA double-strand breaks (DSBs) are formed in meiosis, so their repair the homologous recombination (HR) pathway will lead to crossover formation, which is essential for successful chromosomes segregation. HR contains two sub pathways: synthesis dependent strand annealing (SDSA) that creates non-crossover, and double Holliday junction (dHJ) generates crossovers. RAD-51 a protein formation of all products HR, as it assembles on processed DSB, allowing invasion ssDNA into region...
Replication Protein A (RPA) is a critical complex that acts in replication and promotes homologous recombination by allowing recombinase recruitment to processed DSB ends. Most organisms possess three RPA subunits (RPA1, RPA2, RPA3) form trimeric for viability. The Caenorhabditis elegans genome encodes RPA-1, RPA-2 an paralog RPA-4. In our analysis, we determined germline normal repair of meiotic DSBs. Interestingly, RPA-1 but not essential somatic replication, contrast other require both...
Faithful chromosome segregation into gametes depends on Spo11-induced DNA double-strand breaks (DSBs). These yield single-stranded 3′ tails upon resection to promote crossovers (COs). While early Mre11-dependent end is the predominant pathway in most organisms, Exo1 or Dna2/BLM can also contribute efficient processing of meiotic DSBs. Although its enzymatic activity has been thoroughly dissected, temporal dynamics underlying Spo11 have remained mostly elusive. We show that, Caenorhabditis...
Identifying protein localization is a useful tool in analyzing function. Using GFP-fusion tags, researchers can study the function of endogenous proteins living tissue. However, these tags are considerably large, making them difficult to insert, and they potentially affect normal proteins. To improve on drawbacks, we have adopted split sfGFP system for studying Caenorhabditis elegans germline. This divides "super folder" GFP into 2 fragments, allowing use CRISPR/Cas9 tag more easily with...
Defects in crossover (CO) formation during meiosis are a leading cause of birth defects, embryonic lethality, and infertility. In wide range species, maternal aging increases aneuploidy decreases oocyte quality. C. elegans which produce oocytes throughout the first half adulthood, both quality meiotic errors. Phenotypes mutations genes encoding double-strand break (DSB)-associated proteins get more severe with age suggesting that early reflects particularly sensitive node reproductive worm....
In meiotic prophase I, homologous chromosome pairing is promoted through movement mediated by nuclear envelope proteins, microtubules, and dynein. After proper homologue has been established, the synaptonemal complex (SC) assembles along paired homologues, stabilizing their interaction allowing for crossing over to occur. Previous studies have shown that perturbing leads defects SC polycomplex formation. We show FKB-6 plays a role in assembly required timely double-strand break repair...
Abstract Meiosis is a highly regulated process, partly due to the need break and then repair DNA as part of meiotic program. Post-translational modifications are widely used during events regulate steps such protein complex formation, checkpoint activation, attenuation. In this paper, we investigate how proteins that obligatory components SUMO (small ubiquitin-like modifier) pathway, one post-translational modification, affect Caenorhabditis elegans germline. We show UBC-9, E2 conjugation...
Abstract Meiosis is a tightly regulated process requiring coordination of diverse events. A conserved ERK/MAPK-signaling cascade plays an essential role in the regulation meiotic progression. The Thousand And One kinase (TAO) MAPK kinase, which unknown. We have analyzed functions KIN-18, homolog mammalian TAO kinases, Caenorhabditis elegans. found that KIN-18 for normal progression; mutants exhibit accelerated recombination as detected both by analysis intermediates and crossover outcome. In...
Accumulation of DNA-RNA hybrids in the form R-loops can result replication-transcription conflict that leads to formation DNA double strand breaks (DSBs). Using null mutants for two Caenorhabditis elegans genes encoding RNaseH1 and RNaseH2, we identify novel effects R-loop accumulation germline. leads, as expected, replication stress, followed by DSBs. A subset these DSBs are irreparable. However, unlike irreparable generated other systems, which trigger permanent cell cycle arrest, germline...
Abstract During meiotic prophase I, sister chromatid cohesion is established in a way that supports the assembly of synaptonemal complex (SC). The SC connects homologous chromosomes, directing recombination to create crossovers. In this paper, we identify two proteins cooperate import and load cohesins, thus indirectly promoting assembly. AKIR-1 protein with previously identified role disassembly. akir-1 mutants have no obvious defects cohesion. We ima-2, gene encoding for an α-importin...
To maintain the integrity of genome, meiotic DNA double strand breaks (DSBs) need to form by meiosis-specific nuclease Spo11 and be repaired homologous recombination. One class products formed recombination are crossovers, which required for proper chromosome segregation in first division. The synaptonemal complex (SC) is a protein structure that connects chromosomes during prophase I. assembly SC important recombination, crossover formation, subsequent segregation. Here we identify...
ABSTRACT Faithful meiotic segregation requires pairwise alignment of the homologous chromosomes and Synaptonemal Complex assembly (SC) at their interface. Here, we investigate on new factors that promote coordinate these events during C. elegans meiosis. We identify BRA-2 ( B MP R eceptor A ssociated family member 2) as an interactor HIM-17, previously shown to double-strand break formation. found loss bra-2 specifically impairs synapsis licensing without affecting homologs recognition, SC...
Abstract Akirin, a conserved metazoan protein, functions in muscle development flies and mice. However, this was only tested the rodent fly model systems. Akirin shown to act with chromatin remodeling complexes transcription established as downstream target of NFκB pathway. Here we show role for Caenorhabditis elegans Akirin/AKIR-1 body length regulation through different localizes somatic tissues throughout C. elegans, including nuclei. In agreement its other systems, loss function mutants...
DNA double-strand breaks (DSBs) are toxic lesions that every cell must accurately repair in order to survive. The of DSBs is an integral part a life cycle and can lead lethality if repaired incorrectly. Laser microirradiation established technique which has been used yeast, mammalian culture, Drosophila culture study the regulation DSB repair. Up our studies, this method not adapted for use whole, live, multicellular organism vivo. We have recently shown system be recruitment vital proteins...