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A Genome-Wide Screen for Genes Affecting Spontaneous Direct-Repeat Recombination inSaccharomyces cerevisiae
- Source :
- G3 : Genes, Genomes, Genetics, 10(6), 1858-1867. GENETICS SOCIETY AMERICA, G3: Genes, Genomes, Genetics, Vol 10, Iss 6, Pp 1853-1867 (2020), G3: Genes|Genomes|Genetics
- Publication Year :
- 2020
- Publisher :
- Oxford University Press (OUP), 2020.
-
Abstract
- Homologous recombination is an important mechanism for genome integrity maintenance, and several homologous recombination genes are mutated in various cancers and cancer-prone syndromes. However, since in some cases homologous recombination can lead to mutagenic outcomes, this pathway must be tightly regulated, and mitotic hyper-recombination is a hallmark of genomic instability. We performed two screens inSaccharomyces cerevisiaefor genes that, when deleted, cause hyper-recombination between direct repeats. One was performed with the classical patch and replica-plating method. The other was performed with a high-throughput replica-pinning technique that was designed to detect low-frequency events. This approach allowed us to validate the high-throughput replica-pinning methodology independently of the replicative aging context in which it was developed. Furthermore, by combining the two approaches, we were able to identify and validate 35 genes whose deletion causes elevated spontaneous direct-repeat recombination. Among these are mismatch repair genes, the Sgs1-Top3-Rmi1 complex, the RNase H2 complex, genes involved in the oxidative stress response, and a number of other DNA replication, repair and recombination genes. Since several of our hits are evolutionary conserved, and repeated elements constitute a significant fraction of mammalian genomes, our work might be relevant for understanding genome integrity maintenance in humans.
- Subjects :
- Genome instability
Saccharomyces cerevisiae Proteins
DNA Repair
DNA repair
Saccharomyces cerevisiae
homologous recombination
Computational biology
QH426-470
Genome
03 medical and health sciences
0302 clinical medicine
Genetics
Humans
Direct repeat
Molecular Biology
Gene
Genetics (clinical)
Repetitive Sequences, Nucleic Acid
030304 developmental biology
0303 health sciences
RecQ Helicases
biology
direct repeat
Mutant Screen Report
DNA replication
biology.organism_classification
DNA-Binding Proteins
DNA mismatch repair
dna damage
Homologous recombination
functional genomics
genome stability
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 21601836
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- G3 Genes|Genomes|Genetics
- Accession number :
- edsair.doi.dedup.....3df0fe1eac354975e1ccdb3beae8427e