title: Understanding replication fork progression, stability, and chromosome fragility by exploiting the Suppressor of Underreplication protein.
abstract: There are many layers of regulation governing DNA replication to ensure that genetic information is accurately transmitted from mother cell to daughter cell. While much of the control occurs at the level of origin selection and firing, less is known about how replication fork progression is controlled throughout the genome. In Drosophila polytene cells, specific regions of the genome become repressed for DNA replication, resulting in underreplication and decreased copy number. Importantly, underreplicated domains share properties with common fragile sites. The Suppressor of Underreplication protein SUUR is essential for this repression. Recent work established that SUUR functions by directly inhibiting replication fork progression, raising several interesting questions as to how replication fork progression and stability can be modulated within targeted regions of the genome. Here we discuss potential mechanisms by which replication fork inhibition can be achieved and the consequences this has on genome stability and copy number control.
authors.affiliation: Department of Biology, Whitehead Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Jared T
authors.initials: JT
authors.lastname: Nordman
authors.affiliation: Department of Biology, Whitehead Institute, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Terry L
authors.initials: TL
authors.lastname: Orr-Weaver
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002873:Chromosome Fragility; D017124:Conserved Sequence; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000502:physiology*; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C464850:SuUR protein, Drosophila
keywords: DNA replication; Drosophila; common fragile sites; endocycle; genome stability; polyploidy; underreplication