title: DNA demethylation caused by 5-Aza-2'-deoxycytidine induces mitotic alterations and aneuploidy.
abstract: Aneuploidy, the unbalanced number of chromosomes in a cell, is considered a prevalent form of genetic instability and is largely acknowledged as a condition implicated in tumorigenesis. Epigenetic alterations like DNA hypomethylation have been correlated with cancer initiation/progression. Furthermore, a growing body of evidence suggests the involvement of epigenome-wide disruption as a cause of global DNA hypomethylation in aneuploidy generation.Here, we report that the DNA hypomethylating drug 5-aza-2'-deoxycytidine (DAC), affects the correct ploidy of nearly diploid HCT-116 human cells by altering the methylation pattern of the chromosomes. Specifically, we show that a DAC-induced reduction of 5-Methyl Cytosine at the pericentromeric region of chromosomes correlates with aneuploidy and mitotic defects.Our results suggest that DNA hypomethylation leads to aneuploidy by altering the DNA methylation landscape at the centromere that is necessary to ensure proper chromosomes segregation by recruiting the proteins necessary to build up a functional kinetochore.
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Costa
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Barra
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Lentini
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Palermo, Italy.
authors.forename: Danilo
authors.initials: D
authors.lastname: Cilluffo
authors.affiliation: Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Palermo, Italy.|Centro di OncoBiologia Sperimentale (COBS), Palermo, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Di Leonardo
mesh_terms: D000782:Aneuploidy; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D020732:Cytogenetic Analysis; D019175:DNA Methylation / Q000187:drug effects*; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000187:drug effects*; D011003:Ploidies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine
keywords: 5-aza-2’-deoxycytidine (DAC); Chromosome Section; DNA demethylation; aneuploidy; chromosome methylation pattern