Proceedings of the National Academy of Sciences · 2022 · 14 citations · 33 references
Life SciencesGeneticsMolecular BiologyCancer GeneticsDna RepairDna ReplicationDna Damage RecognitionRepair Of Alkylation DamageAlkyltransferase Repair MechanismsAlkyltransferase-mediated RepairCluster FormationDna Alkylation Damage RepairDna Lesion ProcessingDna Repair By AlkyltransferasesO6-alkylguanine RepairRepair Of O6-alkylguanine Lesions
Significance We directly visualize DNA translocation and lesion recognition by the O 6 -alkylguanine DNA alkyltransferase (AGT). Our data show bidirectional movement of AGT monomers and clusters on undamaged DNA that depended on Zn 2+ occupancy of AGT. A role of cooperative AGT clusters in enhancing lesion search efficiencies by AGT has previously been proposed. Surprisingly, our data show no enhancement of DNA translocation speed by AGT cluster formation, suggesting that AGT clusters may serve a different role in AGT function. Our data support preferential cluster formation by AGT at alkyl lesions, suggesting a role of these clusters in stabilizing lesion-bound complexes. From our data, we derive a new model for the lesion search and repair mechanism of AGT.
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