DNA Polymerase λ, a Novel DNA Repair Enzyme in Human Cells

• Published in: The Journal of biological chemistry Vol. 277; no. 15; p. 13184
• Main Authors: Miguel Garcı́a-Dı́az, Katarzyna Bebenek, Rosario Sabariegos, Orlando Domı́nguez, Josana Rodrı́guez, Tomas Kirchhoff, Esther Garcı́a-Palomero, Angel J. Picher, Raquel Juárez, Jose F. Ruiz, Thomas A. Kunkel, Luis Blanco
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 12.04.2002
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M111601200

DNA polymerase lambda (pol λ) is a novel family X DNA polymerase that has been suggested to play a role in meiotic recombination and DNA repair. The recent demonstration of an intrinsic 5′-deoxyribose-5-phosphate lyase activity in pol λ supports a function of this enzyme in base excision repair. However, the biochemical properties of the polymerization activity of this enzyme are still largely unknown. We have cloned and purified human pol λ to homogeneity in a soluble and active form, and we present here a biochemical description of its polymerization features. In support of a role in DNA repair, pol λ inserts nucleotides in a DNA template-dependent manner and is processive in small gaps containing a 5′-phosphate group. These properties, together with its nucleotide insertion fidelity parameters and lack of proofreading activity, indicate that pol λ is a novel β-like DNA polymerase. However, the high affinity of pol λ for dNTPs (37-fold over pol β) is consistent with its possible involvement in DNA transactions occurring under low cellular levels of dNTPs. This suggests that, despite their similarities, pol β and pol λ have nonredundant in vivo functions.