A5101863026- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Carcinogens and Genotoxicity Assessment
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- Assisted Reproductive Technology and Twin Pregnancy
- Cancer Cells and Metastasis
- Lung Cancer Treatments and Mutations
- Sexual Differentiation and Disorders
- Renal and related cancers
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Adipose Tissue and Metabolism
- Retinoids in leukemia and cellular processes
- DNA and Nucleic Acid Chemistry
- Immune cells in cancer
- Protein Degradation and Inhibitors
- Birth, Development, and Health
Jiangxi Maternal and Child Health Hospital
2024
Chinese Academy of Sciences
2011-2023
Beijing Institute of Genomics
2013-2023
Chinese Academy of Medical Sciences & Peking Union Medical College
2021
University of Chinese Academy of Sciences
2018-2021
Harvard University
2005-2010
Dana-Farber Cancer Institute
2005-2010
Harvard University Press
2006
The ataxia telangiectasia mutant (ATM) protein kinase regulates the cell's response to DNA damage through phosphorylation of proteins involved in cell-cycle checkpoints and repair. However, signal-transduction pathway linking strand breaks activation ATM's activity is not clearly defined. Here, we demonstrate that induces rapid acetylation ATM. This depends on Tip60 histone acetyltransferase (HAT). Suppression blocks prevents ATM-dependent p53 chk2. Further, inactivation sensitizes cells...
AbstractThe ATM protein kinase is essential for cells to repair and survive genotoxic events. The activation of ATM's activity involves acetylation by the Tip60 histone acetyltransferase. In this study, systematic mutagenesis lysine residues was used identify regulatory sites. results a single site at 3016, which located in highly conserved C-terminal FATC domain adjacent domain. Antibodies specific acetyl-lysine 3016 demonstrate rapid (within 5 min) vivo following exposure bleomycin....
Histone acetyltransferases (HATs) regulate transcription, chromatin structure and DNA repair. Here, we utilized a novel HAT inhibitor, anacardic acid, to examine the role of HATs in damage response. Anacardic acid inhibits Tip60 vitro, blocks Tip60‐dependent activation ATM DNA–PKcs protein kinases by vivo. Further, sensitizes human tumor cells cytotoxic effects ionizing radiation. These results demonstrate central for such as regulating inhibitors provide therapeutic approach increasing...
The complexity of chromatin architecture presents a significant barrier to the ability DNA repair machinery access and double-strand breaks (DSBs). Consequently, remodeling landscape adjacent DSBs is vital for efficient repair. Here, we demonstrate that damage destabilizes nucleosomes within regions correspond γ-H2AX domains surrounding DSBs. This nucleosome destabilization an active process requiring ATPase activity p400 SWI/SNF histone acetylation by Tip60 acetyltransferase. recruited...
Members of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, including ATM, DNA-PKcs, Atr, and Trrap proteins, function in signal transduction pathways that activate DNA damage response. PIKK proteins contain a conserved C-terminal FAT/kinase domain/FATC domain structure. The FATC ATM mediates interaction between Tip60, histone acetyltransferase regulates activation ATM. Here, we examined whether domains were also able to interact with Tip60. Deletion blocked Tip60 suppressed...
Abstract Background Checkpoint blockade immunotherapy, represented by PD-1 or PD-L1 antibody treatment, has been of tremendous success in clinical practice. However, the low response rate and lack biomarkers for prediction immune limit application anti-PD-1 immunotherapy. Our recent work showed that a combination low-dose decitabine PD-1-ab significantly improved complete (CR) cHL patients from 32 to 71%, which indicates there is significant correlation between epigenetic regulation Methods...
Induced pluripotent stem cells (iPSCs) and embryonic (ESCs) share many common features, including similar morphology, gene expression in vitro differentiation profiles. However, genomic stability is much lower iPSCs than ESCs. In the current study, we examined whether changes DNA damage repair are responsible for their greater tendency towards mutagenesis.Mouse iPSCs, ESCs fibroblasts were exposed to ionizing radiation (4 Gy) introduce double-strand breaks. At 4 h later, fidelity of was...
The ATM protein kinase is mutated in ataxia telangiectasia, a genetic disease characterized by defective DNA repair, neurodegeneration, and growth factor signaling defects. activity of activated damage, this activation required for cells to survive genotoxic events. In addition well role we now demonstrate novel the retinoic acid (RA)-induced differentiation SH-SY5Y neuroblastoma into post-mitotic, neuronal-like cells. RA rapidly activates kinase, leading ATM-dependent phosphorylation CREB...
Aim: Cancer stem cells (CSCs) drive triple-negative breast cancer recurrence via their properties of self-renewal, invasiveness and radio/chemotherapy resistance. This study examined how CSCs might sustain these properties. Materials & methods: Transcriptomes, DNA methylomes histone modifications were compared between non CSCs. Results: Transcriptome analysis revealed several pathways that activated in CSCs, whereas cell cycle regulation inhibited. Cell development signaling genes...
As a diagnostic biomarker, prostate special antigen (PSA) tests always generate false positive results and lead to unnecessary and/or repeat biopsies. Therefore, there is an urgent need for developing more sensitive, specific biomarkers. We epigenotyped methylated sites in cancer tissues adjacent normal from 66 patients. In comparison with tissues, we observed that were 6 aberrant methylation on the Y-chromosome. further performed pyrosequencing using urine of PCa patients identified one...
Abstract Induced pluripotent stem cells (iPSCs) resemble embryonic (ESCs) in morphology, gene expression and vitro differentiation, raising new hope for personalized clinical therapy. While many efforts have been made to improve reprogramming efficiency, significant problems such as genomic instability of iPSCs need be addressed before In this study, we try figure out the real state their DNA damage response ionizing radiation (IR). We found that iPSC line 3FB4-1 had lower repair ability...
DNA methylation plays an important role for mammalian development. However, it is unclear whether the pattern evolutionarily conserved. The Y chromosome serves as a powerful tool study of human evolution because transferred between males. In this study, based on deep-rooted pedigrees and latest phylogenetic tree, we performed epigenetic analysis from 72 donors. By comparing their respective level, found that was stable among family members haplogroups. Interestingly, two haplogroup-specific...
The DNA methylation of human offspring can change due to the use assisted reproductive technology (ART). In order find differentially methylated regions (DMRs) in ART newborns, cord blood maternal cell contamination and parent background, which will add noise real difference, must be removed. We analyzed newborns’ heel from six families identify DMRs between natural pregnancy genetic model was explored, meanwhile we 32 samples umbilical infants born with those normal confirm differences are...