title: Chronic Replication Problems Impact Cell Morphology and Adhesion of DNA Ligase I Defective Cells.
abstract: Moderate DNA damage resulting from metabolic activities or sub-lethal doses of exogenous insults may eventually lead to cancer onset. Human 46BR.1G1 cells bear a mutation in replicative DNA ligase I (LigI) which results in low levels of replication-dependent DNA damage. This replication stress elicits a constitutive phosphorylation of the ataxia telangiectasia mutated (ATM) checkpoint kinase that fails to arrest cell cycle progression or to activate apoptosis or cell senescence. Stable transfection of wild type LigI, as in 7A3 cells, prevents DNA damage and ATM activation. Here we show that parental 46BR.1G1 and 7A3 cells differ in important features such as cell morphology, adhesion and migration. Comparison of gene expression profiles in the two cell lines detects Bio-Functional categories consistent with the morphological and migration properties of LigI deficient cells. Interestingly, ATM inhibition makes 46BR.1G1 more similar to 7A3 cells for what concerns morphology, adhesion and expression of cell-cell adhesion receptors. These observations extend the influence of the DNA damage response checkpoint pathways and unveil a role for ATM kinase activity in modulating cell biology parameters relevant to cancer progression.
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (CNR), Pavia, Italy; Dipartimento di Biologia e Biotecnologie "L. Spallanzani", Università degli Studi di Pavia, Pavia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Cremaschi
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (CNR), Pavia, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Oliverio
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (CNR), Pavia, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Leva
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (CNR), Pavia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bione
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (CNR), Pavia, Italy; Istituto Universitario di Studi Superiori (IUSS), Pavia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Carriero
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (CNR), Pavia, Italy; Dipartimento di Biologia e Biotecnologie "L. Spallanzani", Università degli Studi di Pavia, Pavia, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Mazzucco
authors.affiliation: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Palamidessi
authors.affiliation: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy; Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milano, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Scita
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (CNR), Pavia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biamonti
authors.affiliation: Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche (CNR), Pavia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Montecucco
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000235:genetics; D048430:Cell Shape / Q000235:genetics*; D004249:DNA Damage; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000172:deficiency / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008856:Microscopy, Fluorescence; D009154:Mutation; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059008:Time-Lapse Imaging / Q000379:methods
chemical_list: C000607892:LIG1 protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D011088:DNA Ligases; D000072481:DNA Ligase ATP