MYST Family Lysine Acetyltransferase Facilitates Ataxia Telangiectasia Mutated (ATM) Kinase-mediated DNA Damage Response in Toxoplasma gondii
| Autor: | Isabelle Coppens, William J. Sullivan, Nathalie Vonlaufen, Arunasalam Naguleswaran |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
DNA Repair
DNA repair DNA damage Molecular Sequence Data Mutant Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases Biochemistry Epigenesis Genetic Histones Animals Humans Amino Acid Sequence Molecular Biology Phylogeny Histone Acetyltransferases Regulation of gene expression biology Kinase Tumor Suppressor Proteins Acetylation Cell Biology Molecular biology Chromatin Recombinant Proteins DNA-Binding Proteins Histone biology.protein Toxoplasma DNA Damage HeLa Cells |
| Zdroj: | Journal of Biological Chemistry. 285:11154-11161 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m109.066134 |
| Popis: | The MYST family of lysine acetyltransferases (KATs) function in a wide variety of cellular operations, including gene regulation and the DNA damage response. Here we report the characterization of the second MYST family KAT in the protozoan parasite Toxoplasma gondii (TgMYST-B). Toxoplasma causes birth defects and is an opportunistic pathogen in the immunocompromised, the latter due to its ability to convert into a latent cyst (bradyzoite). We demonstrate that TgMYST-B can gain access to the parasite nucleus and acetylate histones. Overexpression of recombinant, tagged TgMYST-B reduces growth rate in vitro and confers protection from a DNA-alkylating agent. Expression of mutant TgMYST-B produced no growth defect and failed to protect against DNA damage. We demonstrate that cells overexpressing TgMYST-B have increased levels of ataxia telangiectasia mutated (ATM) kinase and phosphorylated H2AX and that TgMYST-B localizes to the ATM kinase gene. Pharmacological inhibitors of ATM kinase or KATs reverse the slow growth phenotype seen in parasites overexpressing TgMYST-B. These studies are the first to show that a MYST KAT contributes to ATM kinase gene expression, further illuminating the mechanism of how ATM kinase is up-regulated to respond to DNA damage. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|