Dr. Adarsh Kumar

Transforming Protein Structures into Therapeutic Breakthroughs | Structural Biology | Drug Discovery | Crystallographic Fragment Screening | Molecular Biology | Biochemistry

Interlocking activities of DNA polymerase β in the base excision repair pathway


Journal article


Adarsh Kumar, A. Reed, Walter J. Zahurancik, S. Daskalova, S. Hecht, Z. Suo
Proceedings of the National Academy of Sciences of the United States of America, 2022

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APA   Click to copy
Kumar, A., Reed, A., Zahurancik, W. J., Daskalova, S., Hecht, S., & Suo, Z. (2022). Interlocking activities of DNA polymerase β in the base excision repair pathway. Proceedings of the National Academy of Sciences of the United States of America.


Chicago/Turabian   Click to copy
Kumar, Adarsh, A. Reed, Walter J. Zahurancik, S. Daskalova, S. Hecht, and Z. Suo. “Interlocking Activities of DNA Polymerase β in the Base Excision Repair Pathway.” Proceedings of the National Academy of Sciences of the United States of America (2022).


MLA   Click to copy
Kumar, Adarsh, et al. “Interlocking Activities of DNA Polymerase β in the Base Excision Repair Pathway.” Proceedings of the National Academy of Sciences of the United States of America, 2022.


BibTeX   Click to copy

@article{adarsh2022a,
  title = {Interlocking activities of DNA polymerase β in the base excision repair pathway},
  year = {2022},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  author = {Kumar, Adarsh and Reed, A. and Zahurancik, Walter J. and Daskalova, S. and Hecht, S. and Suo, Z.}
}

Abstract

Significance Base 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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