title: Replication, checkpoint suppression and structure of centromeric DNA.
abstract: Human centromeres contain large amounts of repetitive DNA sequences known as α satellite DNA, which can be difficult to replicate and whose functional role is unclear. Recently, we have characterized protein composition, structural organization and checkpoint response to stalled replication forks of centromeric chromatin reconstituted in Xenopus laevis egg extract. We showed that centromeric DNA has high affinity for SMC2-4 subunits of condensins and for CENP-A, it is enriched for DNA repair factors and suppresses the ATR checkpoint to ensure its efficient replication. We also showed that centromeric chromatin forms condensins enriched and topologically constrained DNA loops, which likely contribute to the overall structure of the centromere. These findings have important implications on how chromosomes are organized and genome stability is maintained in mammalian cells.
authors.affiliation: a DNA metabolism laboratory, IFOM, The FIRC institute for Molecular Oncology , Milan , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Romeo
authors.affiliation: a DNA metabolism laboratory, IFOM, The FIRC institute for Molecular Oncology , Milan , Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Falbo
authors.affiliation: a DNA metabolism laboratory, IFOM, The FIRC institute for Molecular Oncology , Milan , Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Costanzo
mesh_terms: D002503:Centromere / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism; D004261:DNA Replication; D006801:Humans
chemical_list: D004247:DNA
keywords: ATR pathway; DNA damage; DNA replication; genomic-genetic instability; stress response