Fig. 6: CAF-1–H3.1–TSK pathway impairment generates Group II–like tandem duplications. | Nature Communications

Fig. 6: CAF-1–H3.1–TSK pathway impairment generates Group II–like tandem duplications.

From: TONSOKU prevents the formation of large tandem duplications and restrains ATR–WEE1 checkpoint activation

Fig. 6: CAF-1–H3.1–TSK pathway impairment generates Group II–like tandem duplications.

A Distribution of tandem duplication sizes in tumors exhibiting a tandem duplicator phenotype5 plotted above the size distribution of tandem duplications observed in tsk-4 plants. Constructed from Supplementary Data 5. B Model of the role of the CAF-1-H3.1-TSK pathway in DNA damage and DDR. CAF-1 loads H3.1 and TSK onto newly replicated DNA, which, when DNA damage is encountered, facilitates DNA repair. This minimizes replication stress and DDR activation, which also depend on TOP1α relieving torsional stress. When TSK function is lost, replication stress increases as damage either goes unrepaired or becomes more severe. This in turn increases ATR-WEE1 DDR pathway activation to a level that, when damaged DNA is repaired, results in tandem duplications. Sufficiently high DDR activation can induce programmed cell death and give rise to developmental phenotypes. Panel created in BioRender. Thomson, G. (2025) https://BioRender.com/l4mxike.

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