7rbn
Human DNA polymerase beta crosslinked complex, 20 min Ca to Mg exchange
Structural highlights
FunctionDPOLB_HUMAN Repair polymerase that plays a key role in base-excision repair. Has 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity that removes the 5' sugar phosphate and also acts as a DNA polymerase that adds one nucleotide to the 3' end of the arising single-nucleotide gap. Conducts 'gap-filling' DNA synthesis in a stepwise distributive fashion rather than in a processive fashion as for other DNA polymerases.[1] [2] [3] [4] Publication Abstract from PubMedSignificanceBase 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 beta (Polbeta), 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 Polbeta 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 Polbeta complexes and proposed a detailed chemical mechanism for Polbeta's 5'-deoxyribose-5-phosphate lyase activity. Interlocking activities of DNA polymerase beta in the base excision repair pathway.,Kumar A, Reed AJ, Zahurancik WJ, Daskalova SM, Hecht SM, Suo Z Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2118940119. doi: , 10.1073/pnas.2118940119. Epub 2022 Mar 1. PMID:35238634[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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