Local chromatin structure at the ribosomal DNA causes replication fork pausing and genome instability in the absence of the S. cerevisiae DNA helicase Rrm3p.
Lack of the yeast Rrm3p DNA helicase causes replication defects at multiple sites within ribosomal DNA (rDNA), including at the replication fork barrier (RFB). These defects were unaltered in rrm3 sir2 cells. When the RFB binding Fob1p was deleted, rrm3-generated defects at the RFB were eliminated, but defects at other rDNA sites were not affected. Thus, specific protein-DNA complexes make replication Rrm3p-dependent. Because rrm3-induced increases in recombination and cell cycle length were only partially suppressed in rrm3 fob1 cells, which still required checkpoint and fork restart activities for viability, non-RFB rrm3-induced defects contribute to rDNA fragility and genome instability.
Torres
Jorge Z
JZ
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA.
Bessler
Jessica B
JB
Zakian
Virginia A
VA
D001665:Binding Sites; D002453:Cell Cycle; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics; D004265:DNA Helicases / Q000235:genetics*; D004261:DNA Replication; D004275:DNA, Ribosomal / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D015180:Electrophoresis, Gel, Two-Dimensional; D017353:Gene Deletion; D042822:Genomic Instability; D006655:Histone Deacetylases / Q000235:genetics; D016296:Mutagenesis; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics
D002843:Chromatin; D004275:DNA, Ribosomal; D004268:DNA-Binding Proteins; C105579:FOB1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases; C459081:Rrm3 protein, S cerevisiae; D004265:DNA Helicases