Systematic analysis of linker histone PTM hotspots reveals phosphorylation sites that modulate homologous recombination and DSB repair.

ABSTRACT: Double strand-breaks (DSBs) of genomic DNA caused by ionizing radiation or mutagenic chemicals are a common source of mutation, recombination, chromosomal aberration, and cell death. Linker histones are DNA packaging proteins with established roles in chromatin compaction, gene transcription, and in homologous recombination (HR)-mediated DNA repair. Using a machine-learning model for functional prioritization of eukaryotic post-translational modifications (PTMs) in combination with genetic and biochemical experiments with the yeast linker histone, Hho1, we discovered that site-specific phosphorylation sites regulate HR and HR-mediated DSB repair. Five total sites were investigated (T10, S65, S141, S173, and S174), ranging from high to low function potential as determined by the model. Of t

SUBMITTER: Mukherjee K 

PROVIDER: S-EPMC6996138 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature