A5057528487- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- CRISPR and Genetic Engineering
- DNA and Nucleic Acid Chemistry
- Chromosomal and Genetic Variations
- Carcinogens and Genotoxicity Assessment
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Genetic factors in colorectal cancer
- Advanced biosensing and bioanalysis techniques
- Genomics and Chromatin Dynamics
- Radiation Therapy and Dosimetry
- Pluripotent Stem Cells Research
- Mitochondrial Function and Pathology
- DNA and Biological Computing
- Genetics, Aging, and Longevity in Model Organisms
- Virus-based gene therapy research
- Genetic Neurodegenerative Diseases
- Ubiquitin and proteasome pathways
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- Polyomavirus and related diseases
- Effects of Radiation Exposure
- Molecular Biology Techniques and Applications
- Cancer Genomics and Diagnostics
University of California, San Francisco
2014-2024
UCSF Helen Diller Family Comprehensive Cancer Center
2018-2021
City College of San Francisco
2018
University of San Francisco
2001
Kettering University
1999
Cornell University
1999
Fondation Jean Dausset-CEPH
1993
Inserm
1993
University of California San Diego Medical Center
1981
University of California, San Diego
1980-1981
Many cancers display both structural (s-CIN) and numerical (w-CIN) chromosomal instabilities. Defective chromosome segregation during mitosis has been shown to cause DNA damage that induces rearrangements of chromosomes (s-CIN). In contrast, whether can disrupt mitotic processes generate whole instability is unknown. Here, we show activation the DNA-damage response (DDR) selectively stabilizes kinetochore-microtubule (k-MT) attachments through Aurora-A PLK1 kinases, thereby increasing...
The ends of chromosomes in mammals, called telomeres, are composed a 6 base pair repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with protein complex shelterin, these telomeric sequences form cap that protects chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually each cell division human somatic cells, limits number times they can divide. extensive involved cancer progression therefore requires cells must acquire ability...
Abstract Purpose: Following cytotoxic therapy, 70% of patients with human papillomavirus (HPV)-positive oropharyngeal head and neck squamous cell carcinoma (HNSCC) are alive at 5 years compared 30% those similar HPV-negative cancer. Loss TGFβ signaling is a poorly studied consequence HPV that could contribute to patient outcome by compromising DNA repair. Experimental Design: Human HNSCC lines (n = 9), patient-derived xenografts tissue microarray 194), TCGA expression data 279), primary...
Abstract Spontaneous telomere loss has been proposed as an important mechanism for initiating the chromosome instability commonly found in cancer cells. We have previously shown that spontaneous a human cell line initiates breakage/fusion/bridge (B/F/B) cycles continue many generations, resulting DNA amplification and translocations on lost its telomere. now extended these studies to determine effect of single stability other chromosomes. Our study showed acquisition during B/F/B occurred...
Reversible transcriptional silencing of genes located near telomeres, termed the telomere position effect (TPE), is well characterized in Saccharomyces cerevisiae. TPE has also been observed human tumor cell lines, but its function remains unknown. To investigate normal mammalian cells, we developed clones mouse embryonic stem (ES) cells that contain single-copy marker integrated adjacent to different telomeres. Analysis these telomeric transgenes demonstrated they were expressed at very low...
Mutant subtypes in the human genetic disease ataxia-telangiectasia (A-T) were classified by means of an assay system that monitors complementation defects DNA synthesis. Anomalies synthesis have been observed previously A-T cells, both their failure to inhibit immediately after exposure ionizing radiation and prolonged S phase. Polyethylene glycol-mediated cell fusion autoradiography combined with selective identification different populations fluorescent colored microspheres determine...
The exquisite sensitivity of mitotic cancer cells to ionizing radiation (IR) underlies an important rationale for the widely used fractionated therapy. However, mechanism this cell cycle-dependent vulnerability is unknown. Here we show that treatment with IR leads chromosome segregation errors in vivo and long-lasting aneuploidy tumour-derived lines. These generate abundance micronuclei predispose chromosomes subsequent catastrophic pulverization thereby independently amplifying...
DNA polymerase theta (POLQ)-mediated end joining (TMEJ) is a distinct pathway for mediating double-strand break (DSB) repair. TMEJ required the viability of BRCA-mutated cancer cells. It crucial to identify tumors that rely on POLQ activity DSB repair, because such are defective in other repair pathways and have predicted sensitivity inhibition therapies produce DSBs. We define here POLQ-associated mutation signatures human cancers, characterized by short insertions deletions specific range...
Among the pleotropic roles of transforming growth factor-β (TGFβ) signaling in cancer, its impact on genomic stability is least understood. Inhibition TGFβ increases use alternative end joining (alt-EJ), an error-prone DNA repair process that typically functions as a "backup" pathway if double-strand break by homologous recombination or nonhomologous compromised. However, consequences this functional relationship therapeutic vulnerability human cancer remain unknown. Here, we show broadly...
Telomeres are essential for protecting the ends of chromosomes and preventing chromosome fusion. Telomere loss has been proposed to play an important role in chromosomal rearrangements associated with tumorigenesis. To determine relationship between telomere instability mammalian cells, we investigated events resulting from introduction a double-strand break near I-SceI endonuclease mouse embryonic stem cells. The inactivation selectable marker gene adjacent as result I-SceI-induced involved...
The addition of new telomeres to the ends broken chromosomes, termed chromosome healing, has been extensively studied in unicellular organisms; however, its role mammalian cell response double-strand breaks is unknown. A system for analysis which involves integration plasmid sequences immediately adjacent a telomere, established mouse embryonic stem cells. This “marked” telomere contains neo gene positive selection G418, an I- Sce I endonuclease recognition sequence introducing breaks, and...
Chromosome instability plays an important role in cancer by promoting the alterations genome required for tumor cell progression. The loss of telomeres that protect ends chromosomes and prevent chromosome fusion has been proposed as one mechanism cells, however, there is little direct evidence to support this hypothesis. To investigate relationship between spontaneous telomere human clones EJ-30 line were isolated which a herpes simplex virus thymidine kinase (HSV-tk) gene was integrated...
The mechanisms of recombination responsible for random integration transfected DNA into the genome normal human cells have been investigated by analysis plasmid-cell junctions. Cell clones containing integrated plasmld sequences were selected morphological transformation primary fibroblasts after transfection with a plasmid simian virus 40 sequences. Nucleotide sequence junctions was performed on cloned fragments sites from two these cell clones. Polymerase chain reaction then flbroblasts to...
Cytomegalovirus virions and dense bodies were purified by sucrose velocity equilibrium centrifugation from the medium of fibroblasts infected with strain AD169. The final virus preparations more than 228-fold respect to cellular proteins as determined double-isotopic labeling at least 1,600-fold on basis changes in ratio total protein particles. content particles approximated that found for other herpesviruses. Twenty polypeptides ranging 22,000 greater 230,000 molecular weight detected...