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- Publisher Website: 10.1073/pnas.1619790114
- Scopus: eid_2-s2.0-85009816965
- PMID: 28049850
- WOS: WOS:000392095800028
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Article: Resolution of single and double Holliday junction recombination intermediates by GEN 1
Title | Resolution of single and double Holliday junction recombination intermediates by GEN 1 |
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Authors | |
Keywords | Repair RecA Recombination RuvC Resolvase |
Issue Date | 2017 |
Citation | Proceedings of the National Academy of Sciences of the United States of America, 2017, v. 114, n. 3, p. 443-450 How to Cite? |
Abstract | Genetic recombination provides an important mechanism for the repair of DNA double-strand breaks. Homologous pairing and strand exchange lead to the formation of DNA intermediates, in which sister chromatids or homologous chromosomes are covalently linked by four-way Holliday junctions (HJs). Depending on the type of recombination reaction that takes place, intermediates may have single or double HJs, and their resolution is essential for proper chromosome segregation. In mitotic cells, double HJs are primarily dissolved by the BLM helicase- TopoisomeraseIIIα-RMI 1-RMI 2 (BTR) complex, whereas single HJs (and double HJs that have escaped the attention of BTR) are resolved by structure-selective endonucleases known as HJ resolvases. These enzymes are ubiquitous in nature, because they are present in bacteriophage, bacteria, archaea, and simple and complex eukaryotes. The human HJ resolvase GEN 1 is a member of the XPG/Rad2 family of 5'-flap endonucleases. Biochemical studies of GEN 1 revealed that it cleaves synthetic DNA substrates containing a single HJ by a mechanism similar to that shown by the prototypic HJ resolvase, Escherichia coli RuvC protein, but it is unclear whether these substrates fully recapitulate the properties of recombination intermediates that arise within a physiological context. Here, we show that GEN 1 efficiently cleaves both single and double HJs contained within large recombination intermediates. Moreover, we find that GEN1 exhibits a weak sequence preference for incision between two G residues that reside in a T-rich region of DNA. These results contrast with those obtained with RuvC, which exhibits a strict requirement for the consensus sequence 5'-A/TTTG/C-3'. |
Persistent Identifier | http://hdl.handle.net/10722/268633 |
ISSN | 2023 Impact Factor: 9.4 2023 SCImago Journal Rankings: 3.737 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Punatar, Rajvee Shah | - |
dc.contributor.author | Martin, Maria Jose | - |
dc.contributor.author | Wyatt, Haley D.M. | - |
dc.contributor.author | Chan, Ying Wai | - |
dc.contributor.author | West, Stephen C. | - |
dc.date.accessioned | 2019-03-25T08:00:16Z | - |
dc.date.available | 2019-03-25T08:00:16Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, 2017, v. 114, n. 3, p. 443-450 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/10722/268633 | - |
dc.description.abstract | Genetic recombination provides an important mechanism for the repair of DNA double-strand breaks. Homologous pairing and strand exchange lead to the formation of DNA intermediates, in which sister chromatids or homologous chromosomes are covalently linked by four-way Holliday junctions (HJs). Depending on the type of recombination reaction that takes place, intermediates may have single or double HJs, and their resolution is essential for proper chromosome segregation. In mitotic cells, double HJs are primarily dissolved by the BLM helicase- TopoisomeraseIIIα-RMI 1-RMI 2 (BTR) complex, whereas single HJs (and double HJs that have escaped the attention of BTR) are resolved by structure-selective endonucleases known as HJ resolvases. These enzymes are ubiquitous in nature, because they are present in bacteriophage, bacteria, archaea, and simple and complex eukaryotes. The human HJ resolvase GEN 1 is a member of the XPG/Rad2 family of 5'-flap endonucleases. Biochemical studies of GEN 1 revealed that it cleaves synthetic DNA substrates containing a single HJ by a mechanism similar to that shown by the prototypic HJ resolvase, Escherichia coli RuvC protein, but it is unclear whether these substrates fully recapitulate the properties of recombination intermediates that arise within a physiological context. Here, we show that GEN 1 efficiently cleaves both single and double HJs contained within large recombination intermediates. Moreover, we find that GEN1 exhibits a weak sequence preference for incision between two G residues that reside in a T-rich region of DNA. These results contrast with those obtained with RuvC, which exhibits a strict requirement for the consensus sequence 5'-A/TTTG/C-3'. | - |
dc.language | eng | - |
dc.relation.ispartof | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.subject | Repair | - |
dc.subject | RecA | - |
dc.subject | Recombination | - |
dc.subject | RuvC | - |
dc.subject | Resolvase | - |
dc.title | Resolution of single and double Holliday junction recombination intermediates by GEN 1 | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1073/pnas.1619790114 | - |
dc.identifier.pmid | 28049850 | - |
dc.identifier.pmcid | PMC5255610 | - |
dc.identifier.scopus | eid_2-s2.0-85009816965 | - |
dc.identifier.volume | 114 | - |
dc.identifier.issue | 3 | - |
dc.identifier.spage | 443 | - |
dc.identifier.epage | 450 | - |
dc.identifier.eissn | 1091-6490 | - |
dc.identifier.isi | WOS:000392095800028 | - |
dc.identifier.issnl | 0027-8424 | - |