{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Uphoff S"],"funding":["Natural Sciences and Engineering Research Council of Canada (NSERC)","Fonds de recherche du Quebec-Nature et technologies","Medical Research Council","Sir Henry Wellcome Fellowship","NIH","Wellcome Trust","NIGMS NIH HHS","Biotechnology and Biological Sciences Research Council"],"pagination":["1094-7"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4827329"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["351(6277)"],"pubmed_abstract":["Cells rely on the precise action of proteins that detect and repair DNA damage. However, gene expression noise causes fluctuations in protein abundances that may compromise repair. For the Ada protein in Escherichia coli, which induces its own expression upon repairing DNA alkylation damage, we found that undamaged cells on average produce one Ada molecule per generation. Because production is stochastic, many cells have no Ada molecules and cannot induce the damage response until the first expression event occurs, which sometimes delays the response for generations. This creates a subpopulation of cells with increased mutation rates. Nongenetic variation in protein abundances thus leads to genetic heterogeneity in the population. Our results further suggest that cells balance reliable repair against toxic side effects of abundant DNA repair proteins."],"journal":["Science (New York, N.Y.)"],"pubmed_title":["Stochastic activation of a DNA damage response causes cell-to-cell mutation rate variation."],"pmcid":["PMC4827329"],"funding_grant_id":["1514510","099204","R01 GM081563","MR/K01577X/1","091911","GM095784","099204/Z/12Z","R01 GM095784","91911","200782/Z/16/Z","BB/I004785/1"],"pubmed_authors":["Paulsson J","Okumus B","Sherratt DJ","Uphoff S","Lord ND","Potvin-Trottier L"],"additional_accession":[]},"is_claimable":false,"name":"Stochastic activation of a DNA damage response causes cell-to-cell mutation rate variation.","description":"Cells rely on the precise action of proteins that detect and repair DNA damage. However, gene expression noise causes fluctuations in protein abundances that may compromise repair. For the Ada protein in Escherichia coli, which induces its own expression upon repairing DNA alkylation damage, we found that undamaged cells on average produce one Ada molecule per generation. Because production is stochastic, many cells have no Ada molecules and cannot induce the damage response until the first expression event occurs, which sometimes delays the response for generations. This creates a subpopulation of cells with increased mutation rates. Nongenetic variation in protein abundances thus leads to genetic heterogeneity in the population. Our results further suggest that cells balance reliable repair against toxic side effects of abundant DNA repair proteins.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Mar","modification":"2025-04-18T16:20:40.832Z","creation":"2019-03-27T03:11:43Z"},"accession":"S-EPMC4827329","cross_references":{"pubmed":["26941321"],"doi":["10.1126/science.aac9786"]}}