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

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

  • Sci Adv. 2025 Dec 19;11(51):eady2104. doi: 10.1126/sciadv.ady2104.
Qi Li 1,  Chenhui Zhao 1,  Yiyi Guo 1,  Yuxue Bai 1,  Jie Liu 1,  Xu Jin 1,  Yue Yuan 1,  Yannick Jacob 2 3,  Jie Dong 1
Affiliations

Affiliations

  • 1 Institute of Crop Science, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China.
  • 2 Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA.
  • 3 Yale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA.
PMID: 41406205 DOI: 10.1126/sciadv.ady2104
Abstract

Histone variants play crucial roles in DNA replication and repair. The plant TONSOKU (TSK) requires histone H3.1 unmethylated at lysine 27 for DNA repair at replication forks, but how TSK is recruited to double-strand break (DSB) sites remains unclear. In this study, we show that the leucine-rich repeat (LRR) domain of TSK recognizes the N-terminal tails of histone variants H2A.X and H2A.W-key for DNA repair in euchromatin and heterochromatin, respectively-but not the H2A.Z variant. A unique motif containing multiple basic and acidic residues (BAR motif) in H2A.Z prevents TSK binding. Moreover, disrupting TSK-H2A.X/W binding impairs TSK-mediated DNA repair. Genetic analyses reveal functional complementation between H2A.X and H2A.W in DNA repair, with the H2A.X N terminus being essential. This study reveals a previously unrecognized, H2A.X/W-dependent mechanism for recruiting the DNA repair protein TSK, highlighting the critical role of their N-terminal tails in plant DNA repair.

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