title: DNA damage and Repair Modify DNA methylation and Chromatin Domain of the Targeted Locus: Mechanism of allele methylation polymorphism.
abstract: We characterize the changes in chromatin structure, DNA methylation and transcription during and after homologous DNA repair (HR). We find that HR modifies the DNA methylation pattern of the repaired segment. HR also alters local histone H3 methylation as well chromatin structure by inducing DNA-chromatin loops connecting the 5' and 3' ends of the repaired gene. During a two-week period after repair, transcription-associated demethylation promoted by Base Excision Repair enzymes further modifies methylation of the repaired DNA. Subsequently, the repaired genes display stable but diverse methylation profiles. These profiles govern the levels of expression in each clone. Our data argue that DNA methylation and chromatin remodelling induced by HR may be a source of permanent variation of gene expression in somatic cells.
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Istituto di Endocrinologia ed Oncologia Sperimentale del C.N.R., Università Federico II, 80131 Napoli, Italy.
authors.forename: Giusi
authors.initials: G
authors.lastname: Russo
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Istituto di Endocrinologia ed Oncologia Sperimentale del C.N.R., Università Federico II, 80131 Napoli, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Landi
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Istituto di Endocrinologia ed Oncologia Sperimentale del C.N.R., Università Federico II, 80131 Napoli, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pezone
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Istituto di Endocrinologia ed Oncologia Sperimentale del C.N.R., Università Federico II, 80131 Napoli, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Morano
authors.affiliation: Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy.
authors.forename: Candida
authors.initials: C
authors.lastname: Zuchegna
authors.affiliation: Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Romano
authors.affiliation: Epigenetics Division, TopoGEN, Inc., 27960 CR319, Buena Vista, Colorado, 81211, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Muller
authors.affiliation: Institute of Cancer Research, Columbia University Medical Center, New York, New York, 10032, USA.
authors.forename: Max E
authors.initials: ME
authors.lastname: Gottesman
authors.affiliation: Dipartimento di Biologia, Università Federico II, 80126 Napoli, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Porcellini
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Istituto di Endocrinologia ed Oncologia Sperimentale del C.N.R., Università Federico II, 80131 Napoli, Italy.
authors.forename: Enrico V
authors.initials: EV
authors.lastname: Avvedimento
mesh_terms: D000483:Alleles; D002843:Chromatin; D004249:DNA Damage; D019175:DNA Methylation; D004260:DNA Repair; D006657:Histones / Q000235:genetics; D006801:Humans; D008745:Methylation
chemical_list: D002843:Chromatin; D006657:Histones