title: Deregulated DNA polymerase beta induces chromosome instability and tumorigenesis.
abstract: To reach the biological alterations that characterize cancer, the genome of tumor cells must acquire increased mutability resulting from a malfunction of a network of genome stability systems, e.g., cell cycle arrest, DNA repair, and high accuracy of DNA synthesis during DNA replication. Numeric chromosomal imbalance, referred to as aneuploidy, is the most prevalent genetic changes recorded among many types of solid tumors. We report here that ectopic expression in cells of DNA polymerase beta, an error-prone enzyme frequently over-regulated in human tumors, induces aneuploidy, an abnormal localization of the centrosome-associated gamma-tubulin protein during mitosis, a deficient mitotic checkpoint, and promotes tumorigenesis in nude immunodeficient mice. Thus, we find that alteration of polymerase beta expression appears to induce major genetic changes associated with a malignant phenotype.
authors.affiliation: Group Instabilité génétique et cancer, Institut de Pharmacologie et de Biologie Structurale, CNRS UPR 9062, 31077 Toulouse, cedex 4, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bergoglio
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Pillaire
authors.forename: Magali
authors.initials: M
authors.lastname: Lacroix-Triki
authors.forename: Brigitte
authors.initials: B
authors.lastname: Raynaud-Messina
authors.forename: Yvan
authors.initials: Y
authors.lastname: Canitrot
authors.forename: Anne
authors.initials: A
authors.lastname: Bieth
authors.forename: Michèle
authors.initials: M
authors.lastname: Garès
authors.forename: Michel
authors.initials: M
authors.lastname: Wright
authors.forename: Georges
authors.initials: G
authors.lastname: Delsol
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Loeb
authors.forename: Christophe
authors.initials: C
authors.lastname: Cazaux
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Hoffmann
mesh_terms: D000782:Aneuploidy; D000818:Animals; D016466:CHO Cells; D002869:Chromosome Aberrations; D006224:Cricetinae; D019951:DNA Polymerase beta / Q000096:biosynthesis* / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008938:Mitosis / Q000235:genetics; D009374:Neoplasms, Experimental / Q000201:enzymology* / Q000235:genetics*; D051381:Rats; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D019951:DNA Polymerase beta