title: Inactivation of the budding yeast cohesin loader Scc2 alters gene expression both globally and in response to a single DNA double strand break.
abstract: Genome integrity is fundamental for cell survival and cell cycle progression. Important mechanisms for keeping the genome intact are proper sister chromatid segregation, correct gene regulation and efficient repair of damaged DNA. Cohesin and its DNA loader, the Scc2/4 complex have been implicated in all these cellular actions. The gene regulation role has been described in several organisms. In yeast it has been suggested that the proteins in the cohesin network would effect transcription based on its role as insulator. More recently, data are emerging indicating direct roles for gene regulation also in yeast. Here we extend these studies by investigating whether the cohesin loader Scc2 is involved in regulation of gene expression. We performed global gene expression profiling in the absence and presence of DNA damage, in wild type and Scc2 deficient G2/M arrested cells, when it is known that Scc2 is important for DNA double strand break repair and formation of damage induced cohesion. We found that not only the DNA damage specific transcriptional response is distorted after inactivation of Scc2 but also the overall transcription profile. Interestingly, these alterations did not correlate with changes in cohesin binding.
authors.affiliation: a Department of Cell and Molecular Biology; Karolinska Institutet ; Stockholm , Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Lindgren
authors.forename: Sara
authors.initials: S
authors.lastname: Hägg
authors.forename: Fosco
authors.initials: F
authors.lastname: Giordano
authors.forename: Johan
authors.initials: J
authors.lastname: Björkegren
authors.forename: Lena
authors.initials: L
authors.lastname: Ström
mesh_terms: D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000172:deficiency* / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors* / Q000172:deficiency* / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D005786:Gene Expression Regulation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D004718:Saccharomycetales / Q000235:genetics / Q000378:metabolism; D000097722:Cohesins
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C410592:SCC2 protein, S cerevisiae
keywords: DI-cohesion, damage induced cohesion; DNA double strand break; DSB DNA, double strand break; FDR, false discovery rate; HO, homothallic switching endonuclease; S, supplementary; SCC, sister chromatid cohesion; SMC, structural maintenance of chromosomes; Scc2; WT, wild type; cohesin network; microarray; transcription profile