A5074860235- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- RNA modifications and cancer
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Mitochondrial Function and Pathology
- Carcinogens and Genotoxicity Assessment
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- Endoplasmic Reticulum Stress and Disease
- RNA Interference and Gene Delivery
- 14-3-3 protein interactions
- Ubiquitin and proteasome pathways
- Immune cells in cancer
- interferon and immune responses
- Polyomavirus and related diseases
- BRCA gene mutations in cancer
- DNA and Nucleic Acid Chemistry
- Viral Infections and Vectors
- Autophagy in Disease and Therapy
- Fungal and yeast genetics research
- MicroRNA in disease regulation
- Mosquito-borne diseases and control
Washington University in St. Louis
2016-2025
Zhujiang Hospital
2024
McGill University
2008-2024
Southern Medical University
2024
Nanchang University
2020-2021
Ann Arbor Center for Independent Living
2012
University of Michigan
2012
University of California, Irvine
2010
Salk Institute for Biological Studies
2005-2009
Torrey Pines Institute For Molecular Studies
2009
ATM has a central role in controlling the cellular responses to DNA damage. It and other phosphoinositide 3-kinase-related kinases (PIKKs) have giant helical HEAT repeat domains their amino-terminal regions. The functions of these PIKKs are not well understood. activation response damage appears be regulated by Mre11-Rad50-Nbs1 (MRN) complex, although exact functional relationship between MRN complex is uncertain. Here we show that two pairs repeats fission yeast (Tel1) interact with an...
Abstract The breast cancer susceptibility proteins BRCA1 and BRCA2 have emerged as key stabilizing factors for the maintenance of replication fork integrity following stress. In their absence, stalled forks are extensively degraded by MRE11 nuclease, leading to chemotherapeutic sensitivity. Here we report that BRCA prevent nucleolytic degradation protecting undergone reversal upon drug treatment. unprotected regressed arms reversed entry point in BRCA-deficient cells. CtIP protein initiates...
BRCA1 is an important mediator of the DNA damage response, which promotes homologous recombination (HR) and antagonizes 53BP1-dependent non-homologous end joining in S/G2 phase. But how this achieved remains unclear. Here, we report that E3 ubiquitin ligase UHRF1 (Ubiquitin-like, with PHD RING finger domains 1) directly participates interplay between 53BP1. Mechanistically, recruited to double-strand breaks (DSBs) by S phase, requires BRCT domain phosphorylated Ser674 UHRF1. Subsequently,...
Dynamic regulation of RNF168-mediated ubiquitylation histone H2A Lys13,15 (H2AK13,15ub) at DNA double-strand breaks (DSBs) is crucial for preventing aberrant repair and maintaining genome stability. However, it remains unclear which deubiquitylating enzyme (DUB) removes H2AK13,15ub. Here we show that USP51, a previously uncharacterized DUB, deubiquitylates H2AK13,15ub regulates damage response. USP51 depletion results in increased spontaneous foci elevated levels H2AK15ub impairs...
Abstract Glioblastoma stem cells (GSCs) play a key role in glioblastoma (GBM) resistance to temozolomide (TMZ) chemotherapy. With the increase research on tumour microenvironment, exosomes secreted by GSCs have become new focus GBM research. However, molecular mechanism which affect drug via remains unclear. Using bioinformatics analysis, we identified specific expression of ABCB4 GSCs. Subsequently, established GSC cell lines and used ultracentrifugation extract exosomes. We conducted vitro...
Abstract Interferon-induced transmembrane protein 3 (IFITM3) has been previously verified to be an endosomal that prevents viral infection. Recent findings suggested IFITM3 as a key factor in tumor invasion and progression. To clarify the role molecular mechanism of Glioblastoma multiforme (GBM) progression, we investigated expression glioma datasets culled from The Cancer Genome Atlas (TCGA) Chinese Glioma (CGGA). Primary GBM stem cells (GSCs) were cultured identified vitro....
Ataxia telangiectasia (A-T) mutated (ATM) is a key deoxyribonucleic acid (DNA) damage signaling kinase that regulates DNA repair, cell cycle checkpoints, and apoptosis. The majority of patients with A-T, cancer-prone neurodegenerative disease, present null mutations in Atm. To determine whether the functions ATM are mediated solely by its activity, we generated two mouse models containing single, catalytically inactivating point In this paper, show that, contrast to Atm-null mice, both...
Protein ubiquitination plays an important role in activating the DNA damage response and maintaining genomic stability. In to double-strand breaks (DSBs), a cascade occurs at lesions. Here, we show that checkpoint with Forkhead-associated (FHA) RING finger domain protein (CHFR), E3 ubiquitin ligase, is recruited DSBs by poly(ADP-ribose) (PAR). At DSBs, CHFR regulates first wave of ubiquitination. Moreover, ubiquitinates PAR polymerase 1 (PARP1) chromatin-associated PARP1 vivo. Thus, these...
Exo1-mediated resection of DNA double-strand break ends generates 3′ single-stranded overhangs required for homology-based repair and activation the ATR-dependent checkpoint. Despite its critical importance in inducing overall damage response, mechanisms regulation Exo1 pathway remain incompletely understood. Here, we identify ring-shaped clamp PCNA as a new factor pathway. Using mammalian cells, Xenopus nuclear extracts purified proteins, show that after damage, loads onto breaks promotes...
Abstract Nonsense-mediated RNA decay (NMD) is recognized as an surveillance pathway that targets aberrant mRNAs with premature translation termination codons (PTC) for degradation, however, its molecular mechanisms and roles in health disease remain incompletely understood. In this study, we developed a novel reporter system to accurately measure NMD activity individual cells. A genome-wide CRISPR-Cas9 knockout screen using identified NMD-promoting factors, including multiple components of...
Using a nucleus-free DNA replication system we have investigated the roles of Xenopus ATR (XATR) and Hus1 (Xhus1) as checkpoint sensors. Like XATR, Xhus1 is required for checkpoint-dependent phosphorylation Xchk1 associates with chromatin in an initiation-dependent manner. While removal protein A inhibits association both XATR Xhus1, polymerase α only disrupts Xhus1. In addition, are independent each other. Finally, like unperturbed S phase dissociates from following completion replication....
Abstract In response to DNA double-strand breaks or oxidative stress, ATM-dependent damage (DDR) is activated maintain genome integrity. However, it remains elusive whether and how single-strand (SSBs) activate ATM. Here, we provide direct evidence in Xenopus egg extracts that ATM-mediated DDR by a defined SSB structure. Our mechanistic studies reveal APE1 promotes the SSB-induced ATM through exonuclease activity recruitment sites. protein can form oligomers absence of directly stimulate...
We previously used a soluble cell-free system derived from Xenopus eggs to investigate the role of protein phosphatase 2A (PP2A) in chromosomal DNA replication. found that immunodepletion PP2A or inhibition by okadaic acid (OA) inhibits initiation replication preventing loading factor Cdc45 onto prereplication complexes. Evidence was provided counteracts an inhibitory kinase phosphorylates and inactivates crucial factor. Here, we report effect OA is abolished caffeine, inhibitor checkpoint...
Spatiotemporal protein reorganization at DNA damage sites induced by genotoxic chemotherapies is crucial for response (DDR), which influences treatment directing cancer cell fate. This process orchestrated valosin-containing (VCP), an AAA+ ATPase that extracts polyubiquinated chromatin proteins and facilitates their turnover. However, because of the essential pleiotropic effects VCP in global proteostasis, it remains challenging practically to understand target its DDR-specific functions. We...