Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage
Holliday junctions (HJs) are key DNA intermediates in homologous recombination. They link homologous DNA strands and have to be faithfully removed for proper DNA segregation and genome integrity. Here, we present the crystal structure of human HJ resolvase GEN1 complexed with DNA at 3.0 Å resolution...
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doaj-0c21a1bbf3684234b3e1e9ac9419e3a92021-05-05T00:10:40ZengeLife Sciences Publications LtdeLife2050-084X2015-12-01410.7554/eLife.12256Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavageShun-Hsiao Lee0Lissa Nicola Princz1Maren Felizitas Klügel2Bianca Habermann3Boris Pfander4Christian Biertümpfel5Department of Structural Cell Biology, Molecular Mechanisms of DNA Repair, Max Planck Institute of Biochemistry, Martinsried, GermanyDepartment of Molecular Cell Biology, DNA Replication and Genome Integrity, Max Planck Institute of Biochemistry, Martinsried, GermanyDepartment of Structural Cell Biology, Molecular Mechanisms of DNA Repair, Max Planck Institute of Biochemistry, Martinsried, GermanyComputational Biology, Max Planck Institute of Biochemistry, Martinsried, GermanyDepartment of Molecular Cell Biology, DNA Replication and Genome Integrity, Max Planck Institute of Biochemistry, Martinsried, GermanyDepartment of Structural Cell Biology, Molecular Mechanisms of DNA Repair, Max Planck Institute of Biochemistry, Martinsried, GermanyHolliday junctions (HJs) are key DNA intermediates in homologous recombination. They link homologous DNA strands and have to be faithfully removed for proper DNA segregation and genome integrity. Here, we present the crystal structure of human HJ resolvase GEN1 complexed with DNA at 3.0 Å resolution. The GEN1 core is similar to other Rad2/XPG nucleases. However, unlike other members of the superfamily, GEN1 contains a chromodomain as an additional DNA interaction site. Chromodomains are known for their chromatin-targeting function in chromatin remodelers and histone(de)acetylases but they have not previously been found in nucleases. The GEN1 chromodomain directly contacts DNA and its truncation severely hampers GEN1’s catalytic activity. Structure-guided mutations in vitro and in vivo in yeast validated our mechanistic findings. Our study provides the missing structure in the Rad2/XPG family and insights how a well-conserved nuclease core acquires versatility in recognizing diverse substrates for DNA repair and maintenance.https://elifesciences.org/articles/12256Holliday junction resolvaseGEN1chromodomaincrystal structureprotein-DNA complexYen1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shun-Hsiao Lee Lissa Nicola Princz Maren Felizitas Klügel Bianca Habermann Boris Pfander Christian Biertümpfel |
spellingShingle |
Shun-Hsiao Lee Lissa Nicola Princz Maren Felizitas Klügel Bianca Habermann Boris Pfander Christian Biertümpfel Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage eLife Holliday junction resolvase GEN1 chromodomain crystal structure protein-DNA complex Yen1 |
author_facet |
Shun-Hsiao Lee Lissa Nicola Princz Maren Felizitas Klügel Bianca Habermann Boris Pfander Christian Biertümpfel |
author_sort |
Shun-Hsiao Lee |
title |
Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage |
title_short |
Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage |
title_full |
Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage |
title_fullStr |
Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage |
title_full_unstemmed |
Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage |
title_sort |
human holliday junction resolvase gen1 uses a chromodomain for efficient dna recognition and cleavage |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2015-12-01 |
description |
Holliday junctions (HJs) are key DNA intermediates in homologous recombination. They link homologous DNA strands and have to be faithfully removed for proper DNA segregation and genome integrity. Here, we present the crystal structure of human HJ resolvase GEN1 complexed with DNA at 3.0 Å resolution. The GEN1 core is similar to other Rad2/XPG nucleases. However, unlike other members of the superfamily, GEN1 contains a chromodomain as an additional DNA interaction site. Chromodomains are known for their chromatin-targeting function in chromatin remodelers and histone(de)acetylases but they have not previously been found in nucleases. The GEN1 chromodomain directly contacts DNA and its truncation severely hampers GEN1’s catalytic activity. Structure-guided mutations in vitro and in vivo in yeast validated our mechanistic findings. Our study provides the missing structure in the Rad2/XPG family and insights how a well-conserved nuclease core acquires versatility in recognizing diverse substrates for DNA repair and maintenance. |
topic |
Holliday junction resolvase GEN1 chromodomain crystal structure protein-DNA complex Yen1 |
url |
https://elifesciences.org/articles/12256 |
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