6XBU

polymerase domain of polymerase-theta

Summary for 6XBU

• Entry DOI: 10.2210/pdb6xbu/pdb
• Descriptor: DNA polymerase theta, DNA (5'-D(P*GP*TP*CP*AP*TP*TP*G)-3'), RNA (5'-R(P*CP*CP*AP*AP*UP*GP*A)-3'), ... (4 entities in total)
• Functional Keywords: replication, dna binding protein, dna binding protein-dna-rna complex, dna binding protein/dna/rna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 82482.81

Authors

Chen, X.,Pomerantz, R.,Zhao, J. (deposition date: 2020-06-07, release date: 2021-06-09, Last modification date: 2023-10-18)

Primary citation

Chandramouly, G.,Zhao, J.,McDevitt, S.,Rusanov, T.,Hoang, T.,Borisonnik, N.,Treddinick, T.,Lopezcolorado, F.W.,Kent, T.,Siddique, L.A.,Mallon, J.,Huhn, J.,Shoda, Z.,Kashkina, E.,Brambati, A.,Stark, J.M.,Chen, X.S.,Pomerantz, R.T.
Pol theta reverse transcribes RNA and promotes RNA-templated DNA repair.
Sci Adv, 7:-, 2021

PubMed Abstract: 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 Polθ reverse transcribes RNA, similar to retroviral reverse transcriptases (RTs). Polθ exhibits a significantly higher velocity and fidelity of deoxyribonucleotide incorporation on RNA versus DNA. The 3.2-Å crystal structure of Polθ 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 Polθ promotes RNA-templated DNA repair in mammalian cells. These findings suggest that Polθ was selected to accommodate template ribonucleotides during DNA repair.

PubMed: 34117057
DOI: 10.1126/sciadv.abf1771

Experimental method

X-RAY DIFFRACTION (3.29 Å)