7RBI

Human DNA polymerase beta crosslinked complex, 20 s Ca to Mg exchange

Summary for 7RBI

• Entry DOI: 10.2210/pdb7rbi/pdb
• Descriptor: DNA polymerase beta, DNA (5'-D(*GP*TP*CP*GP*G)-3'), DNA (5'-D(*GP*CP*TP*GP*AP*TP*GP*CP*GP*CP*C)-3'), ... (9 entities in total)
• Functional Keywords: protein-dna crosslink, polymerase, lyase, drp, transferase, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 50404.45

Authors

Kumar, A. (deposition date: 2021-07-06, release date: 2022-03-09, Last modification date: 2024-11-06)

Primary citation

Kumar, A.,Reed, A.J.,Zahurancik, W.J.,Daskalova, S.M.,Hecht, S.M.,Suo, Z.
Interlocking activities of DNA polymerase beta in the base excision repair pathway.
Proc.Natl.Acad.Sci.USA, 119:e2118940119-e2118940119, 2022

PubMed 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.

PubMed: 35238634
DOI: 10.1073/pnas.2118940119

Experimental method

X-RAY DIFFRACTION (1.93 Å)