Annotation:
DNA-protein crosslinks (DPCs) are a specific type of damage where DNA and a nearby protein become covalently bound. Persisting DPCs interfere with fundamental genetic processes such as DNA replication and transcription. We showed that ZEB covalently traps DNA METHYLTRANSFERASE 1 (MET1) and causes massive accumulation of its DPCs at repetitive
45S rDNA arrays. The understudied mechanism of ZEB-induced DPC repair and the complexity of DNA damage repair pathways prompted us to design a
HYPERSENSITIVE TO ZEBULARINE (
HZE) forward-directed genetic screen. In this study, we show the importance of homologous recombination (HR) factor RTEL1 and microhomology-mediated end joining (MMEJ) polymerase TEB in the repair of MET1-DPCs. Moreover, genetic interaction and sensitivity assays showed the interdependency of SMC5/6 complex, HR, and MMEJ in the homology-directed repair of MET1-DPCs in Arabidopsis. Altogether, we provide evidence that MET1-DPC repair in plants is more complex than originally expected.
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