A5101977491- DNA Repair Mechanisms
- Cancer therapeutics and mechanisms
- Polyomavirus and related diseases
- DNA and Nucleic Acid Chemistry
- PARP inhibition in cancer therapy
- Cancer-related Molecular Pathways
- Advanced X-ray and CT Imaging
- Virus-based gene therapy research
- Molecular Biology Techniques and Applications
- Cancer Research and Treatments
National Cancer Institute
2023-2025
Center for Cancer Research
2023-2025
DNA-protein cross-links (DPCs) are among the most detrimental genomic lesions. They ubiquitously produced by formaldehyde (FA), and failure to repair FA-induced DPCs blocks chromatin-based processes, leading neurodegeneration cancer. The type, structure, of remain largely unknown. Here, we profiled proteome found that flap endonuclease 1 (FEN1) resolves DPCs. We revealed FA also damages DNA bases adjoining DPCs, DPC-conjugated 5′ structures via base excision (BER) pathway. FEN1 repairs...
Topoisomerase III-beta (Top3b) reduces nucleic acid torsional stress and intertwining generated during RNA DNA metabolism while protecting the genome from pathological R-loops, which otherwise result in breakage instability. By studying Top3b knockout mice (Top3b-KO), we find that loss of accelerates development spontaneous lymphoid tumors arising spleens lymph nodes, organs with prominent expression. Aging Top3b-KO also display splenomegaly systemic immune alterations including neutrophilia...
We designed and carried out a high-throughput screen for compounds that trap topoisomerase III beta (TOP3B poisons) by developing Comparative Cellular Cytotoxicity Screen. found bisacridine compound NSC690634 thiacyanine NSC96932 preferentially sensitize cell lines expressing TOP3B, indicating they target TOP3B. These TOP3B cleavage complex (TOP3Bcc) in cells vitro predominately act on RNA, leading to high levels of RNA-TOP3Bccs. also leads enhanced R-loops TOP3B-dependent manner....
Abstract DNA-protein crosslinks (DPCs) are among the most ubiquitous and detrimental DNA lesions which arise from exposure to metabolic stresses, drugs, or crosslinking agents such as formaldehyde (FA). FA is a cellular by-product of methanol metabolism, histone demethylation, lipid peroxidation well environmental pollutants. Failure repair FA-induced DPCs blocks nearly all chromatin-based processes including replication transcription, leading immunodeficiencies, neurodegeneration, cancer....