9yoq
Core module of ctSAGA
Structural highlights
FunctionG0S842_CHATD Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates histone H2A to form H2AS128ph (gamma-H2A) at sites of DNA damage, involved in the regulation of DNA damage response mechanism. Required for the control of telomere length and genome stability.[ARBA:ARBA00025079] Publication Abstract from PubMedThe Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, a 1.8 MDa multi-subunit assembly comprising 19 subunits, is required for RNA polymerase II transcription in eukaryotes. The complex consists of four modules: transcription-associated protein 1 (Tra1), core, deubiquitination (DUB), and histone acetyltransferase (HAT). Although the structures of the Tra1, core, and DUB modules have been determined, the overall architecture of the HAT module remained elusive due to its inherent flexibility. To address this, we conducted cryo-electron microscopy (cryo-EM) analyses on SAGA purified from the thermophilic fungus Chaetomium thermophilum, yielding structures of Tra1 and core modules at 2.6 A and three of the four HAT subunits at 3.7 A. The structure of the HAT module was informative about the aspects of histone acetylation and the interface of HAT-core modules, contradicting earlier AlphaFold predictions. Our structure-guided genetic and biochemical analyses confirmed the roles of Ada1 and Spt7 in anchoring the HAT module within the SAGA complex. Structure of the transcriptional co-activator SAGA complex, including the histone acetyltransferase module.,Mattoo RUH, Chen DH, Bushnell DA, Tamir S, Kornberg RD Mol Cell. 2025 Nov 18:S1097-2765(25)00866-4. doi: 10.1016/j.molcel.2025.10.025. PMID:41260211[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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