A5068262437- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Carcinogens and Genotoxicity Assessment
- Bacterial Genetics and Biotechnology
- Plant Genetic and Mutation Studies
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Radiation Therapy and Dosimetry
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Biochemical and Molecular Research
- Radiation Effects and Dosimetry
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Advanced X-ray Imaging Techniques
- Protein Structure and Dynamics
- RNA Interference and Gene Delivery
- Cancer Research and Treatments
- Microtubule and mitosis dynamics
- Genomic variations and chromosomal abnormalities
- Cancer therapeutics and mechanisms
- Acute Lymphoblastic Leukemia research
Lawrence Berkeley National Laboratory
2009-2023
University of California, Berkeley
1995-2004
University of North Carolina at Chapel Hill
1993
Stanford University
1971-1982
Blue Mountain Community Foundation
1981
The ability to express or deplete proteins in living cells is crucial for the study of biological processes. Viral vectors are often useful deliver DNA constructs that difficult transfect by other methods. Lentiviruses have additional advantage being able integrate into genomes non-dividing mammalian cells. However, existing viral expression systems generally require different vector backbones cDNA, small hairpin RNA (shRNA) microRNA (miRNA) and provide limited drug selection markers....
In normal human cells, damage due to ultraviolet light is preferentially removed from active genes by nucleotide excision repair (NER) in a transcription-coupled (TCR) process that requires the gene products defective Cockayne syndrome (CS). Oxidative damage, including thymine glycols, shown be TCR cells individuals and xeroderma pigmentosum (XP)-A, XP-F, XP-G patients who have NER defects but not severe CS. Thus, of oxidative an XPG function distinct its endonuclease activity. These results...
Cells from patients with Cockayne syndrome (CS), which are sensitive to killing by UV although overall damage removal appears normal, specifically defective in repair of actively transcribed genes. Because several CS strains display cross-sensitivity ionizing radiation, we examined whether radiation-induced active genes is preferentially repaired normal cells and the radiosensitivity can be explained a defect this process. We found that was more rapidly transcriptionally metallothionein IIA...
An assay that allows measurement of absolute induction frequencies for DNA double-strand breaks (dsbs) in defined regions the genome and quantitates rejoining correct ends has been used to study repair dsbs normal human fibroblasts after x-irradiation. The approach involves hybridization single-copy probes Not I restriction fragments separated according size by pulsed-field gel electrophoresis. Induction is quantitated from decrease intensity hybridizing fragment an accumulation a smear...
The DNA polymerase I-deficient mutant polA1 is shown to perform an increased amount of UV-stimulated repair synthesis relative its pol(+) parent. In contrast, a recA recB double found little detectable synthesis. Analysis the density distribution sheared reveals that none in this strain large patches previously demonstrated by us wild-type strains. These results are interpreted terms model involving both I and rec system excision-repair process, with performing efficient short patch enzymes...
Xeroderma pigmentosum (XP) patients have defects in nucleotide excision repair (NER), the versatile pathway that removes UV-induced damage and other bulky DNA adducts. Patients with Cockayne syndrome (CS), another rare sun-sensitive disorder, are specifically defective preferential removal of from transcribed strand active genes, a process known as transcription-coupled repair. These two disorders usually clinically genetically distinct, but complementation analyses assigned few CS to XP...
The relative effectiveness of high-energy neon and iron ions for the production DNA double-strand breaks was measured in one transformed nontransformed human fibroblast cell line using pulsed-field gel electrophoresis. released from plug (fraction activity released: FAR) as well size distribution entering were used to compare effects heavy-ion exposure with X-ray exposure. Both methods gave similar results, indicating distributions over megabase-pair distances heavy X rays. biological (RBE)...
As part of the Nucleotide Excision Repair (NER) process, endonuclease XPG is involved in repair helix-distorting DNA lesions, but protein has also been implicated several other systems, complicating genotype-phenotype relationship patients. Defects can cause either cancer-prone condition xeroderma pigmentosum (XP) alone, or XP combined with severe neurodevelopmental disorder Cockayne Syndrome (CS), infantile lethal cerebro-oculo-facio-skeletal (COFS) syndrome, characterized by dramatic...
Xeroderma pigmentosum group G (XPG) protein is both a functional partner in multiple DNA damage responses (DDR) and pathway coordinator structure-specific endonuclease nucleotide excision repair (NER). Different mutations the XPG gene ERCC5 lead to either of two distinct human diseases: Cancer-prone xeroderma (XP-G) or fatal neurodevelopmental disorder Cockayne syndrome (XP-G/CS). To address enigmatic structural mechanism for these differing disease phenotypes XPG’s role DDRs, here we...
Human positive cofactor 4 (PC4) is a transcriptional coactivator with highly conserved single-strand DNA (ssDNA) binding domain of unknown function. We identified PC4 as suppressor the oxidative mutator phenotype Escherichia coli fpg mutY mutant and demonstrate that this suppression requires its ssDNA activity. Saccharomyces cerevisiae mutants lacking their ortholog Sub1 are sensitive to hydrogen peroxide exhibit spontaneous peroxide-induced hypermutability. expression suppresses sensitivity...
Processivity clamps such as proliferating cell nuclear antigen (PCNA) and the checkpoint sliding clamp Rad9/Rad1/Hus1 (9-1-1) act versatile scaffolds in coordinated recruitment of proteins involved DNA replication, cell-cycle control, repair. Association handoff DNA-editing enzymes, flap endonuclease 1 (FEN1), with are key processes biology, which incompletely understood from a mechanistic point view. We have used an integrative computational experimental approach to define assemblies FEN1...