Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition

The adaptive prokaryotic immune system CRISPR-Cas provides RNA-mediated protection from invading genetic elements. The fundamental basis of the system is the ability to capture small pieces of foreign DNA for incorporation into the genome at the CRISPR locus, a process known as Adaptation, which is...

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Main Authors: Rollie, Clare, Schneider, Stefanie, Brinkmann, Anna Sophie, Bolt, Edward L., White, Malcolm F.
Format: Article
Published: eLife Sciences Publications 2015
Online Access:https://eprints.nottingham.ac.uk/31325/
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author Rollie, Clare
Schneider, Stefanie
Brinkmann, Anna Sophie
Bolt, Edward L.
White, Malcolm F.
author_facet Rollie, Clare
Schneider, Stefanie
Brinkmann, Anna Sophie
Bolt, Edward L.
White, Malcolm F.
author_sort Rollie, Clare
building Nottingham Research Data Repository
collection Online Access
description The adaptive prokaryotic immune system CRISPR-Cas provides RNA-mediated protection from invading genetic elements. The fundamental basis of the system is the ability to capture small pieces of foreign DNA for incorporation into the genome at the CRISPR locus, a process known as Adaptation, which is dependent on the Cas1 and Cas2 proteins. We demonstrate that Cas1 catalyses an efficient trans-esterification reaction on branched DNA substrates, which represents the reverse- or disintegration reaction. Cas1 from both Escherichia coli and Sulfolobus solfataricus display sequence specific activity, with a clear preference for the nucleotides flanking the integration site at the leader-repeat 1 boundary of the CRISPR locus. Cas2 is not required for this activity and does not influence the specificity. This suggests that the inherent sequence specificity of Cas1 is a major determinant of the adaptation process.
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spelling nottingham-313252020-05-04T17:14:57Z https://eprints.nottingham.ac.uk/31325/ Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition Rollie, Clare Schneider, Stefanie Brinkmann, Anna Sophie Bolt, Edward L. White, Malcolm F. The adaptive prokaryotic immune system CRISPR-Cas provides RNA-mediated protection from invading genetic elements. The fundamental basis of the system is the ability to capture small pieces of foreign DNA for incorporation into the genome at the CRISPR locus, a process known as Adaptation, which is dependent on the Cas1 and Cas2 proteins. We demonstrate that Cas1 catalyses an efficient trans-esterification reaction on branched DNA substrates, which represents the reverse- or disintegration reaction. Cas1 from both Escherichia coli and Sulfolobus solfataricus display sequence specific activity, with a clear preference for the nucleotides flanking the integration site at the leader-repeat 1 boundary of the CRISPR locus. Cas2 is not required for this activity and does not influence the specificity. This suggests that the inherent sequence specificity of Cas1 is a major determinant of the adaptation process. eLife Sciences Publications 2015-08-18 Article PeerReviewed Rollie, Clare, Schneider, Stefanie, Brinkmann, Anna Sophie, Bolt, Edward L. and White, Malcolm F. (2015) Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition. eLife . ISSN 2050-084X http://elifesciences.org/content/early/2015/08/17/eLife.08716 doi:10.7554/eLife.08716 doi:10.7554/eLife.08716
spellingShingle Rollie, Clare
Schneider, Stefanie
Brinkmann, Anna Sophie
Bolt, Edward L.
White, Malcolm F.
Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition
title Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition
title_full Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition
title_fullStr Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition
title_full_unstemmed Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition
title_short Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition
title_sort intrinsic sequence specificity of the cas1 integrase directs new spacer acquisition
url https://eprints.nottingham.ac.uk/31325/
https://eprints.nottingham.ac.uk/31325/
https://eprints.nottingham.ac.uk/31325/