Dual RNA 3’-end processing of H2A.X messenger RNA maintains DNA damage repair throughout the cell cycle

Abstract Phosphorylated H2A.X is a critical chromatin marker of DNA damage repair (DDR) in higher eukaryotes. However, gene expression remains relatively uncharacterised. Replication-dependent (RD) histone genes generate poly(A)- mRNA encoding new histones to package during replication. In contrast, replication-independent (RI) synthesise poly(A)+ throughout the cell cycle, translated into variants that confer specific epigenetic patterns on chromatin. Remarkably H2AFX , H2A.X, hybrid gene, generating both and isoforms. Here we report selective removal either isoform reveals different effects types. some cells, RD generates sufficient for deposition onto DDR associated cells making predominantly require this de novo synthesis, required efficient DDR. This highlights importance differential 3’-end processing maintenance effective