title: Homeotic proteins participate in the function of human-DNA replication origins.
abstract: Recent evidence points to homeotic proteins as actors in the crosstalk between development and DNA replication. The present work demonstrates that HOXC13, previously identified as a new member of human DNA replicative complexes, is a stable component of early replicating chromatin in living cells: it displays a slow nuclear dynamics due to its anchoring to the DNA minor groove via the arginine-5 residue of the homeodomain. HOXC13 binds in vivo to the lamin B2 origin in a cell-cycle-dependent manner consistent with origin function; the interaction maps with nucleotide precision within the replicative complex. HOXC13 displays in vitro affinity for other replicative complex proteins; it interacts also in vivo with the same proteins in a cell-cycle-dependent fashion. Chromatin-structure modifying treatments, disturbing origin function, reduce also HOXC13-origin interaction. The described interactions are not restricted to a single origin nor to a single homeotic protein (also HOXC10 binds the lamin B2 origin in vivo). Thus, HOX complexes probably contribute in a general, structure-dependent manner, to origin identification and assembly of replicative complexes thereon, in presence of specific chromatin configurations.
authors.affiliation: NEST, Scuola Normale Superiore and Istituto Nanoscienze-CNR, Laboratorio di Biologia Molecolare, Scuola Normale Superiore, Pisa, Italy. l.marchetti@sns.it
authors.forename: Laura
authors.initials: L
authors.lastname: Marchetti
authors.forename: Laura
authors.initials: L
authors.lastname: Comelli
authors.forename: Barbara
authors.initials: B
authors.lastname: D'Innocenzo
authors.forename: Luca
authors.initials: L
authors.lastname: Puzzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Luin
authors.forename: Daniele
authors.initials: D
authors.lastname: Arosio
authors.forename: Mariantonietta
authors.initials: M
authors.lastname: Calvello
authors.forename: Ramiro
authors.initials: R
authors.lastname: Mendoza-Maldonado
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Peverali
authors.forename: Fabio
authors.initials: F
authors.lastname: Trovato
authors.forename: Silvano
authors.initials: S
authors.lastname: Riva
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biamonti
authors.forename: Gulnara
authors.initials: G
authors.lastname: Abdurashidova
authors.forename: Fabio
authors.initials: F
authors.lastname: Beltram
authors.forename: Arturo
authors.initials: A
authors.lastname: Falaschi
mesh_terms: D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000032:analysis / Q000378:metabolism; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D034921:Lamin Type B / Q000032:analysis; D051379:Mice; D041681:NIH 3T3 Cells; D018741:Replication Origin
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D034921:Lamin Type B