A5018984777- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Endometriosis Research and Treatment
- Uterine Myomas and Treatments
- PARP inhibition in cancer therapy
- Photosynthetic Processes and Mechanisms
- Carcinogens and Genotoxicity Assessment
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Fungal and yeast genetics research
- Endometrial and Cervical Cancer Treatments
- Alzheimer's disease research and treatments
- Apelin-related biomedical research
- Microtubule and mitosis dynamics
- Tryptophan and brain disorders
- Genetic factors in colorectal cancer
- Coenzyme Q10 studies and effects
- Neuroinflammation and Neurodegeneration Mechanisms
- Biochemical Acid Research Studies
Cygnal Therapeutics (United States)
2021-2024
Massachusetts Institute of Technology
2018-2023
University of Pittsburgh
2015-2019
UPMC Hillman Cancer Center
2013-2016
Abstract The conserved budding yeast Rad51 paralogues, including Rad55, Rad57, Csm2 and Psy3 are indispensable for homologous recombination (HR)-mediated chromosome damage repair. Rad55 Rad57 associated in a heterodimer, while form the Shu complex with Shu1 Shu2. Here we show that bridges an interaction between Rad52 and, using fully reconstituted system, demonstrate synergizes Rad55–Rad57 to promote nucleation of on single-stranded DNA pre-occupied by replication protein A (RPA). csm2–F46A...
The Saccharomyces cerevisiae Shu complex, consisting of Shu1, Shu2, Csm2 and Psy3, promotes error-free homologous recombination (HR) by an unknown mechanism. Recent structural analysis two proteins, has revealed that these proteins are Rad51 paralogues mediate DNA binding this complex. We show in vitro the Csm2–Psy3 heterodimer preferentially binds synthetic forked or 3′-DNA overhang substrates resembling structures used during HR vivo . find interacts with paralogues, Rad55–Rad57 complex...
Pervasive neuroinflammation occurs in many neurodegenerative diseases, including Alzheimer's disease (AD). SPI1/PU.1 is a transcription factor located at genome-wide significant AD-risk locus and its reduced expression associated with delayed onset of AD. We analyzed single-cell transcriptomic datasets from microglia human AD patients found an enrichment PU.1-binding motifs the differentially expressed genes. In hippocampal tissues transgenic mice neurodegeneration, we vastly increased...
Abstract The Saccharomyces cerevisiae Shu2 protein is an important regulator of Rad51, which promotes homologous recombination (HR). functions in the Shu complex with Shu1 and Rad51 paralogs Csm2 Psy3. belongs to SWS1 family, characterized by its SWIM domain (CXC...Xn...CXH), a zinc-binding motif. In humans, interacts paralog SWSAP1. Using genetic evolutionary analyses, we examined role mitotic meiotic processes across eukaryotic lineages. We provide evidence that family contains orthologous...
Abstract Accurate DNA replication is essential for genomic stability and cancer prevention. Homologous recombination important high-fidelity damage tolerance during replication. How the homologous machinery recruited to intermediates unknown. Here, we provide evidence that a Rad51 paralog-containing complex, budding yeast Shu directly recognizes enables of predominantly lagging strand abasic sites. We show complex becomes chromatin associated when cells accumulate sites S phase. also...
Here, we investigate the role of budding yeast Shu complex in promoting homologous recombination (HR) upon replication fork damage. We recently found that stimulates Rad51 filament formation during HR through its physical interactions with Rad55-Rad57. Unlike other factors, mutants are primarily sensitive to replicative stress caused by MMS and not more direct DNA breaks. uncover a novel for repair specific MMS-induced lesions elucidate interplay between translesion synthesis. find promotes...
Acute tryptophan depletion is used to induce low levels of serotonin in the brain. This method has been widely psychiatric studies evaluate effect serotonin, and generally considered a safe reversible procedure. Here we use budding yeast Saccharomyces cerevisiae study effects on growth rate upon exposure DNA-damaging agents. Surprisingly, found that undergoing were more sensitive agents such as methyl methanesulphonate (MMS) hydroxyurea (HU). We this defect was independent several DNA repair...
Endometriosis is a chronic inflammatory disease that affects ∼10 % of women. A significant fraction patients experience limited or no efficacy with current therapies. Tissue adjacent to endometriosis lesions often exhibits increased neurite and vascular density, suggesting pathology involves neurotrophic activity angiogenesis.
Double‐strand breaks (DSBs) are one of the most cytotoxic forms DNA damage. Defects in DSB repair associated with cancer predisposition, as well as, several heritable diseases including Fanconi anemia. Our work has centered around Rad51 paralog function during repair. Importantly, mutations human paralogs found tumors and also lead to Due embryonic lethality mouse knockout models low abundance insolubility proteins, there is very limited understanding how maintain genomic integrity. To...
Abstract Introduction Endometriosis is a chronic inflammatory disease that affects ∼10% of women. A significant fraction patients experience limited or no efficacy with current therapies. Tissue adjacent to endometriosis lesions often exhibits increased neurite and vascular density, suggesting pathology involves neurotrophic activity angiogenesis. Objectives We aim evaluate the potential for key tyrosine-kinase-receptor-coupled molecules contribute endometriosis-associated pain in mice....