A5062870725- DNA Repair Mechanisms
- HIV Research and Treatment
- Cytomegalovirus and herpesvirus research
- Cell death mechanisms and regulation
- Drug Transport and Resistance Mechanisms
- Protist diversity and phylogeny
- Cancer-related Molecular Pathways
- Photosynthetic Processes and Mechanisms
- HIV/AIDS drug development and treatment
- PARP inhibition in cancer therapy
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Blood groups and transfusion
- Metabolomics and Mass Spectrometry Studies
- Analytical Chemistry and Chromatography
- interferon and immune responses
- Immunodeficiency and Autoimmune Disorders
- RNA Research and Splicing
- Immune cells in cancer
- Sirtuins and Resveratrol in Medicine
- Chemical Reactions and Isotopes
- Epigenetics and DNA Methylation
- SARS-CoV-2 and COVID-19 Research
National Center for Immunization and Respiratory Diseases
2025
Centers for Disease Control and Prevention
2025
Emory University
2020-2023
Abstract The ATR kinase, which coordinates cellular responses to DNA replication stress, is also essential for the proliferation of normal unstressed cells. Although its role in stress response well defined, mechanisms by supports cell remain elusive. Here, we show that dispensable viability G0-arrested naïve B However, upon cytokine-induced proliferation, Atr-deficient cells initiate efficiently, but mid-S phase they display dNTP depletion, fork stalling, and failure. Nonetheless,...
Abstract Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) has a dNTPase-independent function in promoting DNA end resection to facilitate double-strand break (DSB) repair by homologous recombination (HR); however, it is not known if upstream signaling events govern this activity. Here, we show that SAMHD1 deacetylated the SIRT1 sirtuin deacetylase, facilitating its binding with ssDNA at DSBs, promote HR. complexes deacetylates conserved lysine 354 (K354) specifically response...
Abstract Despite the abundance of ribonucleoside monophosphates (rNMPs) in DNA, sites rNMP incorporation remain poorly characterized. Here, by using ribose-seq and Ribose-Map techniques, we built analyzed high-throughput sequencing libraries rNMPs derived from mitochondrial nuclear DNA budding fission yeast. We reveal both common unique features among yeast species strains, between wild type different ribonuclease H-mutant genotypes. demonstrate that are not randomly incorporated DNA....
Elevated intracellular levels of dNTPs have been shown to be a biochemical marker cancer cells. Recently, series mutations in the multifunctional dNTP triphosphohydrolase (dNTPase), sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1), reported various cancers. Here, we investigated structure functions SAMHD1 R366C/H mutants, found colon leukemia. Unlike many other cancer-specific mutations, R366 do not alter cellular enzyme. However, mutant proteins exhibit loss...
Ribonucleoside monophosphates (rNMPs) represent the most common non-standard nucleotides found in genome of cells. The distribution rNMPs DNA has been studied only limited genomes. Using ribose-seq protocol and Ribose-Map bioinformatics toolkit, we reveal incorporated into whole a photosynthetic unicellular green alga, Chlamydomonas reinhardtii. We discovered disproportionate incorporation adenosine mitochondrial chloroplast DNA, contrast to nuclear relative corresponding nucleotide content...
Abstract Poly ADP-ribose polymerase (PARP) inhibitors are promising targeted therapy for epithelial ovarian cancer (EOC) with BRCA mutations or defective homologous recombination (HR) repair. However, reversion of mutation and restoration HR repair in EOC lead to PARP inhibitor resistance reduced clinical efficacy inhibitors. We have previously shown that triapine, a small molecule ribonucleotide reductase (RNR), impaired sensitized repair-proficient In this study, we performed silico...
Mutations in sterile alpha motif domain and histidine-aspartate domain-containing protein 1 (SAMHD1) are found a neurodevelopmental disorder, Aicardi-Goutières syndrome, cancers, SAMHD1, which is deoxynucleoside triphosphate (dNTP) triphosphorylase, was identified as myeloid-specific HIV-1 restriction factor. Here, we characterized the enzymology structure of an SAMHD1 ortholog Caenorhabditis elegans, ZK177.8, also reportedly induces developmental defects upon gene knockdown. We ZK177.8...
HIV-1 replication in primary monocyte-derived macrophages (MDMs) is kinetically restricted at the reverse transcription step due to low deoxynucleoside triphosphates (dNTP) pools established by host dNTPase, SAM and HD domain containing protein 1 (SAMHD1). Lentiviruses such as HIV-2 some Simian immunodeficiency virus counteract this restriction using viral X (Vpx), which proteosomally degrades SAMHD1 elevates intracellular dNTP pools. However, how increase after Vpx nondividing MDMs where no...
Summary Ribonucleoside monophosphates (rNMPs) represent the most common non-standard nucleotides found in genomic DNA of cells. The distribution rNMPs has been studied only limited genomes, such as yeast nuclear and mitochondrial DNA, well human DNA. In this study, we used ribose-seq protocol Ribose-Map bioinformatics toolkit to reveal incorporated into whole genome a photosynthetic unicellular green alga, Chlamydomonas reinhardtii . study presents discovery disproportionate incorporation...
The ATR kinase, which coordinates cellular responses to DNA replication stress, is also essential for the proliferation of normal unstressed cells. Although its role in stress response well defined, mechanisms by supports cell remain elusive. Here, we show that dispensable viability G0-arrested naïve B However, upon cytokine-induced proliferation, Atr-deficient cells initiate efficiently early S phase, but mid-S phase they display dNTP depletion, fork stalling, and failure. Nonetheless,...
Elevated intracellular dNTP level is a biochemical marker of cancer cells. Recently, series mutations in highly multi-functional dNTPase, SAMHD1, have been reported various cancers. Here we investigated the role SAMHD1 by characterizing cancer-specific mutations. R366C/H mutants, which were found two types, lost dNTPase activity and their X-ray structures demonstrate absence dGTP substrate active site, likely due to loss interaction with γ-phosphate substrate. The mutants failed reduce...