XLF regulates filament architecture of the XRCC4.ligase IV complex
Open accessAbstract
DNA ligase IV (LigIV) is critical for nonhomologous end joining (NHEJ), the major DNA double-strand break (DSB) repair pathway in human cells, and LigIV activity is regulated by XRCC4 and XLF (XRCC4-like factor) interactions. Here, we employ small angle X-ray scattering (SAXS) data to characterize three-dimensional arrangements in solution for full-length XRCC4, XRCC4 in complex with LigIV tandem BRCT domains and XLF, plus the XRCC4·XLF·BRCT2 complex. XRCC4 forms tetramers mediated through a head-to-head interface, and the XRCC4 C-terminal coiled-coil region folds back on itself to support this interaction. The interaction between XLF and XRCC4 is also mediated via head-to-head interactions. In the XLF·XRCC4·BRCT complex, alternating repeating units of XLF and XRCC4·BRCT place the BRCT domain on one side of the filament. Collective results identify XRCC4 and XLF filaments suitable to align DNA molecules and function to facilitate LigIV end joining required for DSB repair in vivo.
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XLF/Cernunnos joins with XRCC4 to align DNA termini for more efficient end-joining.
“The XRCC4 Like Factor (XLF/Cernunnos) functions biochemically to join with the XRCC4 protein to align DNA termini for more efficient end-joining [66,67].”
From Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis (2012) · cites this paper as [66]
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- Authors
- Hammel, M., Yu, Y., Fang, S., Lees-Miller, S. P., & Tainer, J. A.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- University of Calgary (CA)
- Scripps Research Institute (US)
- Corresponding author
- Hammel, Michal
- Tainer, John A.
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2010-11
- Volume
- 18
- Issue
- 11
- Pages
- 1431-1442
- ISSN
- 0969-2126 (ISSN-L)
- PMC
- PMC3008546
- OpenAlex
- W2013663837
- Cited by
- 116
- References
- 49
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 6 · 2022: 6 · 2021: 9 · 2020: 6 · 2019: 9 · 2018: 10 · 2017: 7 · 2016: 6 · 2015: 9 · 2014: 12 · 2013: 10 · 2012: 13
- FWCI
- 4.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Structure (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (69139, CA92584)
- Canadian Institutes of Health Research
- 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 › Protein Structure and Dynamics
- Keywords
- X-ray luminosity function, XRCC4, DNA ligase IV, non-homologous end joining, DNA double-strand break repair, BRCT domain, protein-protein interaction, coiled coil, tetramerization, DNA end joining, DNA sequence alignment
- MeSH terms
- DNA Ligase ATP, Chromatography, Gel, DNA-Binding Proteins, Humans, Models, Molecular, DNA Ligases, Protein Conformation, DNA Repair Enzymes, Scattering, Small Angle, Molecular Dynamics Simulation
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