Defective ATM-Kap-1-mediated chromatin remodeling impairs DNA repair and accelerates senescence in progeria mouse model.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 23173799.
- Also identified by DOI 10.1111/acel.12035.
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Abstract
ATM-mediated phosphorylation of KAP-1 triggers chromatin remodeling and facilitates the loading and retention of repair proteins at DNA lesions. Mouse embryonic fibroblasts (MEFs) derived from Zmpste24(-/-) mice undergo early senescence, attributable to delayed recruitment of DNA repair proteins. Here, we show that ATM-Kap-1 signaling is compromised in Zmpste24(-/-) MEFs, leading to defective DNA damage-induced chromatin remodeling. Knocking down Kap-1 rescues impaired chromatin remodeling, defective DNA repair and early senescence in Zmpste24(-/-) MEFs. Thus, ATM-Kap-1-mediated chromatin remodeling plays a critical role in premature aging, carrying significant implications for progeria therapy.
Medical subject headings
- Cell Cycle Proteins
- Chromatin Assembly and Disassembly
- DNA
- DNA Repair
- DNA-Binding Proteins
- Fibroblasts
- Nuclear Proteins
- Progeria
- Protein Serine-Threonine Kinases
- Repressor Proteins
- Tumor Suppressor Proteins