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Identification of Holliday junction resolvases from humans and yeast
- Stephen C. Y. Ip, Ulrich Rass, Miguel G. Blanco, Helen R. Flynn, J. Skehel, S. West
- Biology, MedicineNature
- 20 November 2008
The human Holliday junction resolvase, GEN1, and its yeast orthologue, Yen1, were independently identified using two distinct experimental approaches: GEN1 was identified by mass spectrometry following extensive fractionation of HeLa cell-free extracts, whereas Yen1 was detected by screening a yeast gene fusion library for nucleases capable of Holliday junctions resolution.
Functional overlap between the structure-specific nucleases Yen1 and Mus81-Mms4 for DNA-damage repair in S. cerevisiae.
- Miguel G. Blanco, Joao Matos, Ulrich Rass, Stephen C. Y. Ip, S. West
- Biology, MedicineDNA repair
- 4 April 2010
Yen1 can act upon recombination/repair intermediates that arise in MUS81-defective cells following replication fork damage, suggesting that DNA repair in S. cerevisiae can be modelled on the basis of Holliday junctions.
The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates
Ataxia oculomotor apraxia-1 (AOA1) is a neurological disorder caused by mutations in the gene (APTX) encoding aprataxin. Aprataxin is a member of the histidine triad (HIT) family of nucleotide…
Mechanism of Holliday junction resolution by the human GEN1 protein.
This work provides the first biochemical/structural characterization of GEN1, showing that, like the Escherichia coli HJ resolvase RuvC, it binds specifically to HJs and resolves them by a dual incision mechanism in which nicks are introduced in the pair of continuous strands within the lifetime of the GEN1-HJ complex.
Defective DNA Repair and Neurodegenerative Disease
This review focuses on studies defining the molecular defects associated with several human neurological disorders, particularly ataxia with oculomotor apraxia 1 and spinocerebellar atAXia with axonal neuropathy 1.
Rif1 and Rif2 Shape Telomere Function and Architecture through Multivalent Rap1 Interactions
A molecular, biochemical, and functional dissection of the protein backbone at the core of the yeast telosome is provided, revealing tetramerization and polymerization modules that give rise to a higher-order architecture that interlinks Rap1 units.
Resolving branched DNA intermediates with structure-specific nucleases during replication in eukaryotes
- Ulrich Rass
- Biology, MedicineChromosoma
- 6 September 2013
In eukaryotes, multiple structure-specific nucleases have been implicated in the resolution of branched DNA intermediates and it is becoming increasingly clear that, as a group, they reflect the dual function of RuvC in cleaving recombination intermediate and failing replication forks to assist the DNA replication process.
Actions of Aprataxin in Multiple DNA Repair Pathways*
It is suggested that Aprataxin may have a general proofreading function in DNA repair, removing DNA adenylates as they arise during single-strand break repair, double-Strand break Repair, and in base excision repair.
Molecular Mechanism of DNA Deadenylation by the Neurological Disease Protein Aprataxin*
It is shown that APTX acts as a nick sensor, which provides a mechanism to assess the adenylation status of unsealed nicks, and is pinpointed as the first protein to adopt canonical histidine triad-type reaction chemistry for the repair of DNA.
Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1
- Gizem Ölmezer, Maryna Levikova, +4 authors Ulrich Rass
- Biology, MedicineNature communications
- 25 October 2016
This work finds the Dna2 helicase activity acts parallel to homologous recombination in promoting DNA replication and chromosome detachment at mitosis after replication fork stalling, and identifies a non-canonical role for Yen1 in the processing of replication intermediates that is distinct from HJ resolution.