title: Replication fork instability and the consequences of fork collisions from rereplication.
abstract: Replication forks encounter obstacles that must be repaired or bypassed to complete chromosome duplication before cell division. Proteomic analysis of replication forks suggests that the checkpoint and repair machinery travels with unperturbed forks, implying that they are poised to respond to stalling and collapse. However, impaired fork progression still generates aberrations, including repeat copy number instability and chromosome rearrangements. Deregulated origin firing also causes fork instability if a newer fork collides with an older one, generating double-strand breaks (DSBs) and partially rereplicated DNA. Current evidence suggests that multiple mechanisms are used to repair rereplication damage, yet these can have deleterious consequences for genome integrity.
authors.affiliation: Whitehead Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Alexander
authors.affiliation: Whitehead Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
authors.forename: Terry L
authors.initials: TL
authors.lastname: Orr-Weaver
mesh_terms: D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004261:DNA Replication; D056890:Eukaryota / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics*; D018741:Replication Origin / Q000235:genetics*
keywords: break-induced replication; double-strand break repair; gene amplification; homologous recombination; nonhomologous end-joining