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Direct recruitment of TONSOKU by the N-terminal tails of histone variants H2A.X and H2A.W coordinates DNA repair

ABSTRACT: Histone variants play crucial roles in DNA replication and DNA damage repair. Plant TONSOKU (TSK) specifically recognizes unmethylated histone H3.1 to bind post-replicative chromatin for DNA repair, but the precise mechanisms of TSK recruitment to double-stranded break (DSB) sites remain unclear. Here, we discovered that the leucine-rich repeats (LRR) domain of TSK recognizes the N-terminal tail of the histone variant H2A.X, the phosphorylated form of which (also known as γ-H2A.X) is a critical marker of DSBs at both replication forks and euchromatin. Additionally, the LRR domain of TSK recognizes the N-terminal tail of the plant-specific histone H2A variant H2A.W, which is essential for DSB repair in heterochromatin, but not H2A.Z, which primarily regulates gene expression. A motif containing multiple basic and acidic residues (BAR motif), unique to H2A.Z, prevents TSK from binding. Notably, mutations that abolish TSK-H2A.X/W binding interfere with TSK-mediated DNA repair and root development. Genetic analyses indicate that H2A.X and H2A.W are redundantly required for DNA damage repair in vivo, with the N-terminus of H2A.X being particularly indispensable. This study reveals a novel H2A.X/W-dependent mechanism for recruiting the DNA repair protein TSK, highlighting the critical role of their previously uncharacterized N-terminal tails in plants.

ORGANISM(S): Arabidopsis thaliana

PROVIDER: GSE293950 | GEO | 2025/11/18

REPOSITORIES: GEO

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