Structural Basis of UV DNA-Damage Recognition by the DDB1–DDB2 Complex
Open accessAbstract
Ultraviolet (UV) light-induced pyrimidine photodimers are repaired by the nucleotide excision repair pathway. Photolesions have biophysical parameters closely resembling undamaged DNA, impeding discovery through damage surveillance proteins. The DDB1-DDB2 complex serves in the initial detection of UV lesions in vivo. Here we present the structures of the DDB1-DDB2 complex alone and bound to DNA containing either a 6-4 pyrimidine-pyrimidone photodimer (6-4PP) lesion or an abasic site. The structure shows that the lesion is held exclusively by the WD40 domain of DDB2. A DDB2 hairpin inserts into the minor groove, extrudes the photodimer into a binding pocket, and kinks the duplex by approximately 40 degrees. The tightly localized probing of the photolesions, combined with proofreading in the photodimer pocket, enables DDB2 to detect lesions refractory to detection by other damage surveillance proteins. The structure provides insights into damage recognition in chromatin and suggests a mechanism by which the DDB1-associated CUL4 ubiquitin ligase targets proteins surrounding the site of damage.
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DDB2 detects pyrimidine dimers caused by UV light and triggers nucleotide excision DNA repair.
“DDB2 detects pyrimidine dimers caused by UV light and triggers nucleotide excision DNA repair47.”
From A genomics approach reveals insights into the importance of gene losses for mammalian adaptations (2018) · cites this paper as [47]
The Summary and “The overall structure of the DDB1-DDB2 complex” identify DDB2 as an early detector of UV-induced pyrimidine dimers in global-genome nucleotide excision repair. But the latter section says XPC-RAD23B’s arrival triggers recruitment of the repair machinery; it does not establish that DDB2 itself triggers repair. (LLM, conf=0.84)
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- Authors
- Scrima, A., Koníčková, R., Czyzewski, B. K., Kawasaki, Y., Jeffrey, P. D., Groisman, R., Nakatani, Y., Iwai, S., Pavletich, N. P., & Thomä, N. H.
- Affiliations
- Friedrich Miescher Institute (CH)
- Memorial Sloan Kettering Cancer Center (US)
- The University of Osaka (JP)
- Centre National de la Recherche Scientifique (FR)
- Harvard University (US)
- Corresponding author
- Pavletich, Nikola P.
- Thomä, Nicolas H.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 135
- Issue
- 7
- Pages
- 1213-1223
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2676164
- OpenAlex
- W1979417055
- Cited by
- 441
- References
- 6
- Citations by year
- 2026: 19 · 2025: 17 · 2024: 12 · 2023: 30 · 2022: 20 · 2021: 25 · 2020: 20 · 2019: 32 · 2018: 21 · 2017: 29 · 2016: 26 · 2015: 32 · 2014: 35 · 2013: 21 · 2012: 19
- FWCI
- 10.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1725 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- European Molecular Biology Organization
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (120205)
- Paul Scherrer Institut
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- abasic sites, nucleotide excision repair, WD40 domain, DNA minor groove binding, chromatin
- MeSH terms
- Animals, DNA Damage, DNA Repair, DNA-Binding Proteins, Humans, Models, Molecular, Pyrimidine Dimers, Ultraviolet Rays, Xeroderma Pigmentosum, Zebrafish, Zebrafish Proteins
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