A5103910293- DNA Repair Mechanisms
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- Phytochemical and Pharmacological Studies
- Ubiquitin and proteasome pathways
- Plant Molecular Biology Research
- Natural product bioactivities and synthesis
- Phytochemicals and Antioxidant Activities
- RNA Research and Splicing
- Telomeres, Telomerase, and Senescence
- Microtubule and mitosis dynamics
- PARP inhibition in cancer therapy
- Plant Gene Expression Analysis
- Epigenetics and DNA Methylation
- Medicinal plant effects and applications
- Cancer-related Molecular Pathways
- Phytochemistry and Biological Activities
- Chemotherapy-induced cardiotoxicity and mitigation
- Cancer-related gene regulation
- Mitochondrial Function and Pathology
- Photosynthetic Processes and Mechanisms
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- Lipid metabolism and biosynthesis
- Botanical Studies and Applications
University of Chinese Academy of Sciences
2015-2024
Massachusetts General Hospital
2014-2024
MUSC Hollings Cancer Center
2024
Medical University of South Carolina
2024
Harvard University
2013-2024
Northwest Institute of Plateau Biology
2015-2024
Qinghai Tibetan Hospital
2021-2024
Institute of Tibetan Plateau Research
2015-2023
Chinese Academy of Sciences
1999-2023
Duke University
2023
Abstract Posttranslational modifications of proteins by small ubiquitin-like modifiers (SUMOs) regulate protein degradation and localization, protein–protein interaction, transcriptional activity. SUMO E3 ligase functions are executed SIZ1/SIZ2 Mms21 in yeast, the PIAS family members RanBP2, Pc2 human. The Arabidopsis thaliana genome contains only one gene, SIZ1, that is orthologous to yeast SIZ1/SIZ2. Here, we show SIZ1 expressed all plant tissues. Compared with wild type, null mutant...
Alternative lengthening of telomeres (ALT) is a telomerase-independent but recombination-dependent pathway that maintains telomeres. Here, we describe an assay to visualize ALT-mediated telomeric DNA synthesis in ALT-associated PML bodies (APBs) without DNA-damaging agents or replication inhibitors. Using this assay, find ALT occurs through two distinct mechanisms. One the mechanisms requires RAD52, protein implicated break-induced (BIR). We demonstrate RAD52 directly promotes D-loop...
Significance This study shows that Fragile X mental retardation protein (FMRP) promotes messenger RNA (mRNA)-dependent recombination via facilitating ten-eleven translocation 1 (TET1)-mediated mRNA methyl-5-cytosine (m5C) demethylation. Loss of FMRP leads to damage induced m5C and R-loop accumulation at sites active transcription, defective repair, increased radiosensitivity tumor cells. FMRP-dependent demethylation resolving during DNA repair are important for completion the maintenance...
Posttranslational modification of substrates by the small ubiquitin-like modifier, SUMO, regulates diverse biological processes, including transcription, DNA repair, nucleocytoplasmic trafficking, and chromosome segregation. SUMOylation is reversible, several mammalian homologs yeast SUMO-specific protease Ulp1, termed SENPs, have been identified. We demonstrate here that SENP5, a previously uncharacterized Ulp1 homolog, has SUMO C-terminal hydrolase isopeptidase activities. In contrast to...
Abstract Recruitment of DNA repair proteins to damage sites is a critical step for repair. Post-translational modifications at serve as codes recruit specific factors. Here, we show that mRNA locally modified by m 5 C damage. The RNA methyltransferase TRDMT1 recruited promote induction. Loss compromises homologous recombination (HR) and increases cellular sensitivity double-strand breaks (DSBs). In the absence TRDMT1, RAD51 RAD52 fail localize reactive oxygen species (ROS)-induced vitro,...
The phytohormone indole-3-acetic acid (IAA) plays a vital role in plant growth and development as regulator of numerous biological processes. Its biosynthetic pathways have been studied for decades. Recent genetic vitro labeling evidence indicates that IAA Arabidopsis thaliana other plants is primarily synthesized from precursor an intermediate the tryptophan (Trp) pathway. To determine which intermediate(s) acts possible branchpoint Trp-independent biosynthesis plants, we took vivo approach...
Oleanolic acid (OA), asiatic (AA), and maslinic (MA) are ubiquitous isomeric triterpene phytochemicals with many pharmacological effects. To improve their application value, we used lipopolysaccharide (LPS) to induce RAW264.7 cells studied the differences in anti-inflammatory effects of triterpenes according structural differences. MTT, Griess, immunofluorescence assays, ELISA, flow cytometry, Western blotting, were performed. The release LPS-induced pro-inflammatory mediators, such as...
S-Adenosyl-l-methionine:phosphoethanolamine N-methyltransferase (PEAMT; EC 2.1.1.103) catalyzes the key step in choline (Cho) biosynthesis, N-methylation of phosphoethanolamine. Cho is a vital precursor membrane phospholipid phosphatidylcholine, which accounts for 40 to 60% lipids nonplastid plant membranes. Certain plants use produce osmoprotectant glycine betaine, confers resistance salinity, drought, and other stresses. An Arabidopsis mutant, t365, PEAMT gene silenced, was identified...
AbstractPost-translational modification of many transcription factors and cofactors by the small ubiquitin-related modifier SUMO has been correlated with transcriptional repression. Recent investigations molecular mechanisms underlying SUMO-dependent repression have identified diverse chromatin modifying enzymes associated proteins as effectors changes in structure gene expression. A surprising diversity to be recruited promoters a manner, including histone deacetylase HDAC2, demethylase...
Abstract The plant tryptophan (Trp) biosynthetic pathway produces many secondary metabolites with diverse functions. Indole‐3‐acetic acid (IAA), proposed as a derivative from Trp or its precursors, plays an essential role in growth and development. Although the Trp‐dependant Trp‐independent IAA pathways have been proposed, enzymes, reactions regulatory mechanisms are largely unknown. In Arabidopsis , indole‐3‐glycerol phosphate (IGP) is suggested to serve branchpoint component biosynthesis....
The master checkpoint kinase ATR (ATM and Rad3-related) its partner ATRIP (ATR-interacting protein) exist as a complex function together in the DNA damage response. Unexpectedly, we found that stability of ATR–ATRIP is regulated by an unknown independently damage. In search for this regulator ATR–ATRIP, single member NIMA (never mitosis A)-related family, Nek1, critical initiating Upon damage, cells lacking Nek1 failed to efficiently phosphorylate multiple substrates support...
The ATR (ATM [ ataxia telangiectasia -mutated]- and Rad3-related) checkpoint is a crucial DNA damage signaling pathway. While the pathway known to transmit signals through ATR–Chk1 kinase cascade, whether post-translational modifications other than phosphorylation are important for this remains largely unknown. Here, we show that protein SUMOylation plays key role in ATRIP, regulatory partner of ATR, modified by SUMO2/3 at K234 K289. An ATRIP mutant lacking sites fails localize support...
Petanin, an acylated anthocyanin from the Solanaceae family, shows potential in tyrosinase inhibitory activity and anti-melanogenic effects; however, its mechanism remains unclear. Therefore, to investigate underlying of petanin’s effects, enzyme activity, protein expression mRNA transcription melanogenic related signaling pathways zebrafish using network pharmacology, molecular docking dynamics simulation were combined for analysis. The results showed that petanin could inhibit...
DNA damage activates checkpoints that limit the replicative potential of stem cells, including differentiation. These protect against cancer development but also promote tissue aging. Because mice lacking Slug/Snai2 exhibit limited cell activity, luminobasal differentiation, and are protected from mammary cancer, we reasoned Slug might regulate in epithelial cells. Here, show facilitates efficient execution RPA32-mediated response (DDR) signaling. deficiency leads to delayed phosphorylation...
The mismatch repair (MMR) deficiency of cancer cells drives mutagenesis and offers a useful biomarker for immunotherapy. However, many MMR-deficient (MMR-d) tumors do not respond to immunotherapy, highlighting the need alternative approaches target MMR-d cells. Here, we show that inhibition ATR kinase preferentially kills Mechanistically, inhibitor (ATRi) imposes synthetic lethality on by inducing DNA damage in replication- MUS81 nuclease-dependent manner. induced ATRi is colocalized with...
Drugs targeting the DNA damage response (DDR) are widely used in cancer therapy, but resistance to these drugs remains a major clinical challenge. Here, we show that SYCP2, meiotic protein synaptonemal complex, is aberrantly and commonly expressed breast ovarian cancers associated with broad DDR drugs. Mechanistically, SYCP2 enhances repair of double-strand breaks (DSBs) through transcription-coupled homologous recombination (TC-HR). promotes R-loop formation at DSBs facilitates RAD51...