PreprintCited by 20DNA Repair MechanismsEnzyme Structure and FunctionGenomics and Chromatin Dynamics

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Cryo-EM structure of the Spo11 core complex bound to DNA

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Preprint — published as 10.1038/s41594-024-01382-8 · Paper page

Abstract

The DNA double-strand breaks that initiate meiotic recombination are formed by topoisomerase relative Spo11, supported by conserved auxiliary factors. Because high-resolution structural data are lacking, many questions remain about the architecture of Spo11 and its partners and how they engage with DNA. We report cryo-EM structures at up to 3.3 Å resolution of DNA-bound core complexes of Saccharomyces cerevisiae Spo11 with Rec102, Rec104, and Ski8. In these structures, monomeric core complexes make extensive contacts with the DNA backbone and with the recessed 3’-OH and first 5’ overhanging nucleotide, definitively establishing the molecular determinants of DNA end-binding specificity and providing insight into DNA cleavage preferences in vivo. The structures of individual subunits and their interfaces, supported by functional data in yeast, provide insight into the role of metal ions in DNA binding and uncover unexpected structural variation in homologs of the Top6BL component of the core complex.

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Metadata

Authors
Yu, Y., Wang, J., Liu, K., Zheng, Z., Arter, M., Bouuaert, C. C., Pu, S., Patel, D. J., & Keeney, S.
Affiliations
Memorial Sloan Kettering Cancer Center (US)
Corresponding author
  • Patel, Dinshaw J.
  • Keeney, Scott
Venue
Nature Structural & Molecular Biology
Publisher
openRxiv
Published
2023-11-01
Volume
32
Issue
1
Pages
113-124
ISSN
1545-9985 (ISSN-L)
OpenAlex
W4402713468
Cited by
20
References
1
Citations by year
2026: 8 · 2025: 7 · 2024: 5
FWCI
2.72
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Structural & Molecular Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • Digital Access to Libraries (submittedVersion, other-oa)
Funders
  • Howard Hughes Medical Institute (P30 CA08748)
  • Damon Runyon Cancer Research Foundation
  • Memorial Sloan-Kettering Cancer Center (P30-CA08748)
  • National Institutes of Health (CA08748)
  • National Cancer Institute (P30-CA-08748, CA08748, P30CA008748)
  • National Institute of General Medical Sciences (R35GM118092)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD110120)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
Spo11, meiotic recombination, DNA double-strand breaks, DNA cleavage, Saccharomyces cerevisiae

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