title: Genome-wide screen reveals replication pathway for quasi-palindrome fragility dependent on homologous recombination.
abstract: Inverted repeats capable of forming hairpin and cruciform structures present a threat to chromosomal integrity. They induce double strand breaks, which lead to gross chromosomal rearrangements, the hallmarks of cancers and hereditary diseases. Secondary structure formation at this motif has been proposed to be the driving force for the instability, albeit the mechanisms leading to the fragility are not well-understood. We carried out a genome-wide screen to uncover the genetic players that govern fragility of homologous and homeologous Alu quasi-palindromes in the yeast Saccharomyces cerevisiae. We found that depletion or lack of components of the DNA replication machinery, proteins involved in Fe-S cluster biogenesis, the replication-pausing checkpoint pathway, the telomere maintenance complex or the Sgs1-Top3-Rmi1 dissolvasome augment fragility at Alu-IRs. Rad51, a component of the homologous recombination pathway, was found to be required for replication arrest and breakage at the repeats specifically in replication-deficient strains. These data demonstrate that Rad51 is required for the formation of breakage-prone secondary structures in situations when replication is compromised while another mechanism operates in DSB formation in replication-proficient strains.
authors: School of Biology and Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, United States of America.
authors: Yu
authors: Y
authors: Zhang
authors: Natalie
authors: N
authors: Saini
authors: Ziwei
authors: Z
authors: Sheng
authors: Kirill S
authors: KS
authors: Lobachev
mesh_terms: D020087:Alu Elements / Q000235:genetics; D002873:Chromosome Fragility / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D004261:DNA Replication / Q000235:genetics*; D016681:Genome, Fungal / Q000235:genetics; D059765:Homologous Recombination / Q000235:genetics*; D055029:Inverted Repeat Sequences / Q000235:genetics*; D009690:Nucleic Acid Conformation; D059372:Nucleotide Motifs / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics
chemical_list: D051135:Rad51 Recombinase