Summary information and primary citation

PDB-id
7rbh; SNAP-derived features in text and JSON formats; DNAproDB
Class
transferase-DNA
Method
X-ray (1.75 Å)
Summary
Human DNA polymerase beta crosslinked ternary complex 2
Reference
Kumar A, Reed AJ, Zahurancik WJ, Daskalova SM, Hecht SM, Suo Z (2022): "Interlocking activities of DNA polymerase beta in the base excision repair pathway." Proc.Natl.Acad.Sci.USA, 119, e2118940119. doi: 10.1073/pnas.2118940119.
Abstract
SignificanceBase excision repair (BER) is one of the major DNA repair pathways used to fix a myriad of cellular DNA lesions. The enzymes involved in BER, including DNA polymerase β (Polβ), have been identified and characterized, but how they act together to efficiently perform BER has not been fully understood. Through gel electrophoresis, mass spectrometry, and kinetic analysis, we discovered that the two enzymatic activities of Polβ can be interlocked, rather than functioning independently from each other, when processing DNA intermediates formed in BER. The finding prompted us to hypothesize a modified BER pathway. Through conventional and time-resolved X-ray crystallography, we solved 11 high-resolution crystal structures of cross-linked Polβ complexes and proposed a detailed chemical mechanism for Polβ's 5'-deoxyribose-5-phosphate lyase activity.

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