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Structures of the CRISPR genome integration complex.

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Title: Structures of the CRISPR genome integration complex.
Authors: Wright, Addison V., Jun-Jie Liu, Knott, Gavin J., Doxzen, Kevin W., Nogales, Eva, Doudna, Jennifer A.
Source: Science (pre-March 2025). 9/15/2017, Vol. 357 Issue 6356, p1113-1118. 6p. 6 Color Photographs.
Subjects: CRISPRs, Integrase genetics, DNA structure, Integration host factor, Nucleotide sequence, Electron microscopy
Abstract: CRISPR-Cas systems depend on the Cas1-Cas2 integrase to capture and integrate short foreign DNA fragments into the CRISPR locus, enabling adaptation to new viruses. We present crystal structures of Cas1-Cas2 bound to both donor and target DNA in intermediate and product integration complexes, as well as a cryo–electron microscopy structure of the full CRISPR locus integration complex, including the accessory protein IHF (integration host factor). The structures show unexpectedly that indirect sequence recognition dictates integration site selection by favoring deformation of the repeat and the flanking sequences. IHF binding bends the DNA sharply, bringing an upstream recognition motif into contact with Cas1 to increase both the specificity and efficiency of integration. These results explain how the Cas1-Cas2 CRISPR integrase recognizes a sequence-dependent DNA structure to ensure site-selective CRISPR array expansion during the initial step of bacterial adaptive immunity. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Structures of the CRISPR genome integration complex.
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  Data: <searchLink fieldCode="AR" term="%22Wright%2C+Addison+V%2E%22">Wright, Addison V.</searchLink><br /><searchLink fieldCode="AR" term="%22Jun-Jie+Liu%22">Jun-Jie Liu</searchLink><br /><searchLink fieldCode="AR" term="%22Knott%2C+Gavin+J%2E%22">Knott, Gavin J.</searchLink><br /><searchLink fieldCode="AR" term="%22Doxzen%2C+Kevin+W%2E%22">Doxzen, Kevin W.</searchLink><br /><searchLink fieldCode="AR" term="%22Nogales%2C+Eva%22">Nogales, Eva</searchLink><br /><searchLink fieldCode="AR" term="%22Doudna%2C+Jennifer+A%2E%22">Doudna, Jennifer A.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 9/15/2017, Vol. 357 Issue 6356, p1113-1118. 6p. 6 Color Photographs.
– Name: Subject
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  Data: <searchLink fieldCode="DE" term="%22CRISPRs%22">CRISPRs</searchLink><br /><searchLink fieldCode="DE" term="%22Integrase+genetics%22">Integrase genetics</searchLink><br /><searchLink fieldCode="DE" term="%22DNA+structure%22">DNA structure</searchLink><br /><searchLink fieldCode="DE" term="%22Integration+host+factor%22">Integration host factor</searchLink><br /><searchLink fieldCode="DE" term="%22Nucleotide+sequence%22">Nucleotide sequence</searchLink><br /><searchLink fieldCode="DE" term="%22Electron+microscopy%22">Electron microscopy</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: CRISPR-Cas systems depend on the Cas1-Cas2 integrase to capture and integrate short foreign DNA fragments into the CRISPR locus, enabling adaptation to new viruses. We present crystal structures of Cas1-Cas2 bound to both donor and target DNA in intermediate and product integration complexes, as well as a cryo–electron microscopy structure of the full CRISPR locus integration complex, including the accessory protein IHF (integration host factor). The structures show unexpectedly that indirect sequence recognition dictates integration site selection by favoring deformation of the repeat and the flanking sequences. IHF binding bends the DNA sharply, bringing an upstream recognition motif into contact with Cas1 to increase both the specificity and efficiency of integration. These results explain how the Cas1-Cas2 CRISPR integrase recognizes a sequence-dependent DNA structure to ensure site-selective CRISPR array expansion during the initial step of bacterial adaptive immunity. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=125179094
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        Value: 10.1126/science.aao0679
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      – Code: eng
        Text: English
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        PageCount: 6
        StartPage: 1113
    Subjects:
      – SubjectFull: CRISPRs
        Type: general
      – SubjectFull: Integrase genetics
        Type: general
      – SubjectFull: DNA structure
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      – SubjectFull: Integration host factor
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      – SubjectFull: Nucleotide sequence
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      – SubjectFull: Electron microscopy
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      – TitleFull: Structures of the CRISPR genome integration complex.
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            NameFull: Nogales, Eva
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              M: 09
              Text: 9/15/2017
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              Y: 2017
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