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Publication Abstract from PubMed

Genome-embedded ribonucleotides arrest replicative DNA polymerases (Pols) and cause DNA breaks. Whether mammalian DNA repair Pols efficiently use template ribonucleotides and promote RNA-templated DNA repair synthesis remains unknown. We find that human Poltheta reverse transcribes RNA, similar to retroviral reverse transcriptases (RTs). Poltheta exhibits a significantly higher velocity and fidelity of deoxyribonucleotide incorporation on RNA versus DNA. The 3.2-A crystal structure of Poltheta on a DNA/RNA primer-template with bound deoxyribonucleotide reveals that the enzyme undergoes a major structural transformation within the thumb subdomain to accommodate A-form DNA/RNA and forms multiple hydrogen bonds with template ribose 2'-hydroxyl groups like retroviral RTs. Last, we find that Poltheta promotes RNA-templated DNA repair in mammalian cells. These findings suggest that Poltheta was selected to accommodate template ribonucleotides during DNA repair.

Poltheta reverse transcribes RNA and promotes RNA-templated DNA repair.,Chandramouly G, Zhao J, McDevitt S, Rusanov T, Hoang T, Borisonnik N, Treddinick T, Lopezcolorado FW, Kent T, Siddique LA, Mallon J, Huhn J, Shoda Z, Kashkina E, Brambati A, Stark JM, Chen XS, Pomerantz RT Sci Adv. 2021 Jun 11;7(24):eabf1771. doi: 10.1126/sciadv.abf1771. Print 2021 Jun. PMID:34117057^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.