title: Open sesame: activating dormant replication origins in the mouse immunoglobulin heavy chain (Igh) locus.
abstract: Chromosomal DNA replication in mammals initiates from replication origins whose activity differs in accordance with cell type and differentiation state. In addition to origins that are active in unperturbed conditions, chromosomes also contain dormant origins that can become functional in response to certain genotoxic stress conditions. Improper regulation of origin usage can cause genomic instability leading to tumorigenesis. We review findings from recent single-molecule DNA fiber studies examining replication of the mouse immunoglobulin heavy chain (Igh) locus, in which origin activity over a 400kb region is subject to dramatic developmental regulation. Possible models are discussed to explain such differential origin usage, particularly during replication stress conditions that can activate dormant origins.
authors.affiliation: Department of Biochemistry and New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, United States.
authors.forename: James A
authors.initials: JA
authors.lastname: Borowiec
authors.forename: Carl L
authors.initials: CL
authors.lastname: Schildkraut
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004261:DNA Replication; D050438:Genes, Immunoglobulin Heavy Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D051379:Mice; D008957:Models, Genetic; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000378:metabolism; D018741:Replication Origin
chemical_list: D007143:Immunoglobulin Heavy Chains