Practice question

Among histone modifications, phosphorylation uniquely creates rapid, reversible signaling platforms for DNA damage response. Upon double-strand breaks, ATM, ATR and DNA-PK rapidly phosphorylate H2A.X at serine 139, generating γ-H2A.X that spreads megabases around lesions. This phospho-epitope is recognized by BRCT and FHA domains of MDC1, 53BP1 and repair factors, concentrating ubiquitylation and remodeling activities. Unlike acetylation or methylation that modulate transcription, phosphorylation provides high-turnover signal integration, coupling checkpoint activation, cell-cycle arrest and homologous recombination or non-homologous end joining pathway choice.