A5018246911- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Bacterial Genetics and Biotechnology
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- RNA and protein synthesis mechanisms
- Electron Spin Resonance Studies
- CO2 Reduction Techniques and Catalysts
- Genetic factors in colorectal cancer
- Cancer-related Molecular Pathways
- Genomics and Chromatin Dynamics
Vanderbilt University
2022-2024
Massachusetts Institute of Technology
2022
University of New Hampshire
1993
The xeroderma pigmentosum protein A (XPA) and replication (RPA) proteins fulfill essential roles in the assembly of preincision complex nucleotide excision repair (NER) pathway. We have previously characterized two interaction sites, one between XPA N-terminal (XPA-N) disordered domain RPA32 C-terminal (RPA32C), other with DNA binding (DBD) RPA70AB DBDs. Here, we show that mutations inhibit physical either site reduce NER activity biochemical cellular systems. Combining sites leads to an...
Abstract Phagocytosis requires the coordination of various classes receptors and activation multiple signaling programs, culminating in actin cytoskeletal rearrangement ingestion. Given pleiotropic nature events necessary for proper microbial ingestion, identifying molecules that control distinct steps phagocytosis could reveal potential strategies to enhance clearance. PTEN is a lipid/protein phosphatase traditionally recognized as tumor suppressor. While inhibits arms innate immune...
Replication fork reversal is a fundamental process required for resolution of encounters with DNA damage. A key step in the stabilization and eventual reversed forks formation RAD51 nucleoprotein filaments on exposed single strand (ssDNA). To avoid genome instability, are tightly controlled by variety positive negative regulators. RADX (RPA-related RAD51-antagonist X chromosome) recently discovered regulator that binds to ssDNA, directly interacts RAD51, regulates replication...
Abstract Nucleotide excision repair (NER) reduces efficacy of treatment with platinum (Pt)-based chemotherapy by removing Pt lesions from DNA. Previous study has identified that missense mutation or loss the NER genes Excision Repair Cross Complementation Group 1 and 2 (ERCC1 ERCC2) leads to improved patient outcomes after Pt-based chemotherapies. Although most gene alterations found in tumors are mutations, impact mutations remaining nearly 20 is unknown. Towards this goal, we previously...
DNA synthesis during replication begins with the generation of an ∼10-nucleotide primer by primase. Primase contains a redox-active 4Fe-4S cluster in C-terminal domain p58 subunit (p58C). The redox state this can be modulated via transport charge through protein and substrate (redox switching); changes alter ability p58C to associate its substrate. efficiency switching altered mutating tyrosine residues that bridge nucleic acid binding site. Here, we report effects bridging tyrosines...
Abstract The XPA and RPA proteins fulfill essential roles in the assembly of preincision complex nucleotide excision repair pathway. We have previously characterized two interaction surfaces between RPA, with RPA32 RPA70AB subunits. Here we show that mutations individual reduce NER activity biochemical cellular systems, combining domains leads to an additive inhibition NER, suggesting they distinct roles. Our data suggest is important for initial association complexes, while RPA70 needed...
Abstract Nucleotide excision repair (NER) neutralizes treatment with platinum (Pt)-based chemotherapy by removing Pt lesions from DNA. Previous study has identified that missense mutation or loss of either the NER genes Excision Repair Cross Complementation Group 1 and 2 ( ERCC1 ERCC2 ) leads to improved patient outcomes after Pt-based chemotherapies. Although most gene alterations found in tumors are mutations, impact such mutations remaining nearly 20 is unknown. Towards this goal, we...
Replication fork reversal is a fundamental process required for resolution of encounters with DNA damage. A key step in the stabilization and eventual reversed forks formation RAD51 nucleoprotein filaments on exposed ssDNA. To avoid genome instability, are tightly controlled by variety positive negative regulators. RADX recently discovered regulator that binds to ssDNA, directly interacts RAD51, regulates replication context-dependent manner. Here we present structure-based investigation...