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Molecular basis of DNA polymerase ζ’s reverse transcriptase activity

Radhika Malik, Robert Eugene Johnson, Louise Prakash, Satya Prakash, Aneel K. Aggarwal

Revista con revisión por pares

En palabras de los autores

DNA polymerase ζ (Polζ) has emerged as a key reverse transcriptase in RNA-templated double-strand break repair (RT-DSBR), beyond its canonical role in translesion DNA synthesis (TLS). We present here the cryo-EM structure of yeast Polζ (including Rev1) in the act of reverse transcription, wherein the polymerase molds the replicative end of the bound RNA:DNA hybrid into B-like conformation and retains most contacts seen with DNA:DNA. Critically, the polymerase adopts the same conformation as with DNA:DNA, indicating its inherent versatility in accommodating both DNA:DNA and RNA:DNA substrates to preserve genome stability. DNA polymerase ζ (Polζ) functions as a reverse transcriptase in RNA templated double-strand break repair. Here the authors present the cryo-EM structure of Polζ engaged in reverse transcription and reveal that the bound RNA:DNA hybrid is moulded into a B-like conformation while retaining most contacts seen with DNA:DNA.

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Apareció: domingo, 27 de septiembre. Nature Communications. Revista con revisión por pares.

DOI: 10.1038/s41467-026-78032-8