A5036450352- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Cancer therapeutics and mechanisms
- Carcinogens and Genotoxicity Assessment
- Genetic factors in colorectal cancer
- Mesenchymal stem cell research
- Plant Stress Responses and Tolerance
- Advanced biosensing and bioanalysis techniques
- Microtubule and mitosis dynamics
- Tissue Engineering and Regenerative Medicine
- Cancer Genomics and Diagnostics
- Surgical Sutures and Adhesives
- Cancer Cells and Metastasis
- Plant nutrient uptake and metabolism
- Body Contouring and Surgery
- BRCA gene mutations in cancer
- Reconstructive Surgery and Microvascular Techniques
- Polyomavirus and related diseases
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
National Institutes of Health
2008-2023
National Cancer Institute
2013-2023
National Human Genome Research Institute
2017-2022
University of Nevada, Reno
2007-2013
University of Nevada, Las Vegas
2012-2013
Las Vegas Institute
2012
Project Management Institute
2012
The University of Texas Southwestern Medical Center
2011
Neurons harbor high levels of single-strand DNA breaks (SSBs) that are targeted to neuronal enhancers, but the source this endogenous damage remains unclear. Using two systems postmitotic lineage specification-induced pluripotent stem cell-derived neurons and transdifferentiated macrophages-we show thymidine glycosylase (TDG)-driven excision methylcytosines oxidized with ten-eleven translocation enzymes (TET) is a SSBs. Although macrophage differentiation favors short-patch base repair fill...
Abstract Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib has been approved for treatment of advanced ovarian cancer associated with BRCA1 and BRCA2 mutations. - -mutated cells, which are homologous recombination (HR) deficient, hypersensitive to PARPi through the mechanism synthetic lethality. Here we examine effect on HR-proficient cells. Olaparib pretreatment, PARP1 knockdown or Parp1 heterozygosity Brca2 cko/ko mouse embryonic stem cells (mESCs), carrying a null ( ko )...
The nonhomologous end-joining (NHEJ) pathway is essential for radioresistance and lymphocyte-specific V(D)J (variable [diversity] joining) recombination. Defects in NHEJ also impair hematopoietic stem cell (HSC) activity with age but do not affect the initial establishment of HSC reserves. In this paper, we report that, contrast to deoxyribonucleic acid (DNA)–dependent protein kinase catalytic subunit (DNA-PKcs)–null mice, knockin mice DNA-PKcs3A/3A allele, which codes three alanine...
Homologous recombination (HR) is initiated by DNA end resection, a process in which stretches of single-strand (ssDNA) are generated and used for homology search. Factors implicated resection include nucleases MRE11, EXO1, DNA2, ends into 3′ ssDNA overhangs; helicases such as BLM, unwind DNA; other proteins BRCA1 CtIP whose functions remain unclear. CDK-mediated phosphorylation on T847 required to promote whereas CDK-dependent CtIP-S327 interaction with BRCA1. Here, we provide evidence that...
53BP1 is a well-known mediator of the cellular response to DNA damage. Two alternative mechanisms have been proposed explain 53BP1’s interaction with double-strand breaks (DSBs), one by binding methylated histones and other via an RNF8 E3 ligase–dependent ubiquitylation pathway. The formation irradiation-induced foci are both dependent on histone H2AX. To evaluate contribution RNF8-dependent pathway function, we generated knockout mice. We report that deficiency results in defective class...
Topoisomerase II (TOP2) relieves topological stress in DNA by introducing double-strand breaks (DSBs) via a transient, covalently linked TOP2 DNA-protein intermediate, termed cleavage complex (TOP2cc). TOP2ccs are normally rapidly reversible, but can be stabilized poisons, such as the chemotherapeutic agent etoposide (ETO). poisons have shown significant variability their therapeutic effectiveness across different cancers for reasons that remain to determined. One potential explanation...
MDA-MB-435S human breast cancer cells (435S) secrete nucleoside diphosphate kinase (NDPK) that supports metastases and is inhibited by epigallocatechin gallate (EGCG) ellagic acid (EA). We hypothesise 435S cell-secreted NDPK-B tumour formation modulating ATP levels locally to activate endothelial cell (EC) P2Y receptor-mediated angiogenesis. Epigallocatechin (IC50=8–10 μ M) EA (IC50=2–3 suppressed growth, but had less effect on CD31+ EC growth. (IC50=11 (IC50=1 also prevented tubulogenesis...
Background: Adipose-derived stem cells have become the most studied adult cells. The authors examined apoptosis and necrosis rates for adipocyte, stromal vascular fraction, adipose-derived in fresh human lipoaspirates. Methods: Human lipoaspirate (n = 8) was harvested using a standard liposuction technique. Stromal fraction were separated from adipocytes cultured to obtain purified A panel of cell markers used identify surface phenotypes Three distinct subpopulations (CD90+/CD45−,...