title: DNA resection proteins Sgs1 and Exo1 are required for G1 checkpoint activation in budding yeast.
abstract: Double-strand breaks (DSBs) in budding yeast trigger activation of DNA damage checkpoints, allowing repair to occur. Although resection is necessary for initiating damage-induced cell cycle arrest in G2, no role has been assigned to it in the activation of G1 checkpoint. Here we demonstrate for the first time that the resection proteins Sgs1 and Exo1 are required for efficient G1 checkpoint activation. We find in G1 arrested cells that histone H2A phosphorylation in response to ionizing radiation is independent of Sgs1 and Exo1. In contrast, these proteins are required for damage-induced recruitment of Rfa1 to the DSB sites, phosphorylation of the Rad53 effector kinase, cell cycle arrest and RNR3 expression. Checkpoint activation in G1 requires the catalytic activity of Sgs1, suggesting that it is DNA resection mediated by Sgs1 that stimulates the damage response pathway rather than protein-protein interactions with other DDR proteins. Together, these results implicate DNA resection, which is thought to be minimal in G1, as necessary for activation of the G1 checkpoint.
authors.affiliation: Committee on Molecular Pathogenesis and Molecular Medicine, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Fiyinfolu O
authors.initials: FO
authors.lastname: Balogun
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Truman
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kron
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D059766:DNA End-Joining Repair; D004271:DNA, Fungal / Q000235:genetics; D005090:Exodeoxyribonucleases / Q000502:physiology*; D059585:G1 Phase Cell Cycle Checkpoints; D006657:Histones / Q000378:metabolism; D050296:Microbial Viability / Q000528:radiation effects; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D053484:RecQ Helicases / Q000502:physiology*; D051716:Replication Protein A / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D006657:Histones; C082728:RFA1 protein, S cerevisiae; D051716:Replication Protein A; D029701:Saccharomyces cerevisiae Proteins; C069930:rad9 protein; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D005090:Exodeoxyribonucleases; C028450:exodeoxyribonuclease I; C090472:SGS1 protein, S cerevisiae; D053484:RecQ Helicases
keywords: Checkpoint activation; DNA damage; DNA resection; Exo1; G1; Sgs1; Yeast