A Structural Solution for the DNA Polymerase λ-Dependent Repair of DNA Gaps with Minimal Homology
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Human DNA polymerase lambda (Pol lambda) is a family X member with low frameshift fidelity that has been suggested to perform gap-filling DNA synthesis during base excision repair and during repair of broken ends with limited homology. Here, we present a 2.1 A crystal structure of the catalytic core of Pol lambda in complex with DNA containing a two nucleotide gap. Pol lambda makes limited contacts with the template strand at the polymerase active site, and superimposition with Pol beta in a ternary complex suggests a shift in the position of the DNA at the active site that is reminiscent of a deletion intermediate. Surprisingly, Pol lambda can adopt a closed conformation, even in the absence of dNTP binding. These observations have implications for the catalytic mechanism and putative DNA repair functions of Pol lambda.
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Crystal structures reveal that polymerase binding to DNA strongly reshapes the primer-template, for example the backbone at the templating base can be bent by 90°.
“Crystal structures (Refs.15-22 and references therein) reveal that polymerase binding to DNA strongly reshapes the primertemplate, e.g. the backbone at the templating base can be bent by 90°.”
From DNA Replication Fidelity (2004) · cites this paper as [22]
Pol λ has similar base substitution fidelity to Pol β, yet unlike Pol β it is in a closed conformation even without a bound dNTP.
“Also, Pol has similar base substitution fidelity to Pol , yet unlike Pol  it is in a closed conformation even without a bound dNTP (22).”
From DNA Replication Fidelity (2004) · cites this paper as [22]
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- Authors
- Garcia-Diaz, M., Bebenek, K., Krahn, J. M., Blanco, L., Kunkel, T. A., & Pedersen, L. C.
- Affiliations
- National Institutes of Health (US)
- Centro de Biología Molecular Severo Ochoa (ES)
- Corresponding author
- Kunkel, Thomas A
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 13
- Issue
- 4
- Pages
- 561-572
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2026830245
- Cited by
- 126
- References
- 56
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 1 · 2022: 6 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 4 · 2016: 3 · 2015: 6 · 2014: 2 · 2013: 7 · 2012: 5
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- DNA polymerase lambda, base excision repair, crystal structure, catalytic core, polymerase active site, DNA repair
- MeSH terms
- Amino Acid Sequence, Base Sequence, Binding Sites, DNA Repair, Humans, Models, Molecular, Molecular Sequence Data, Molecular Weight, Nucleic Acid Conformation, Protein Binding, Substrate Specificity, Conserved Sequence, Sequence Homology, Amino Acid, Protein Structure, Secondary, Protein Structure, Tertiary, Crystallography, X-Ray, DNA Polymerase beta, Static Electricity
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