Break induced replication in eukaryotes: mechanisms, functions, and consequences. (4th July 2017)

• Record Type: Journal Article
• Authors: Sakofsky, Cynthia J.; Malkova, Anna
• Is Part Of: Critical reviews in biochemistry and molecular biology. Volume 52:Number 4(2017)
• Page Start: 395
• Page End: 413
• Publication Date: 2017-07-04
• Subjects: Break-induced replication -- alternative lengthening of telomeres -- Rad51-dependent break-induced replication -- Rad51-independent break-induced replication -- microhomology-mediated break-induced replication -- half-crossover -- mutation cluster; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Biochemistry -- Periodicals; Molecular Biology -- Periodicals; Review Literature -- Periodicals; 572
• DOI: 10.1080/10409238.2017.1314444
• Languages: English
• ISSNs: 1040-9238

Abstract

Abstract: Break-induced replication (BIR) is an important pathway specializing in repair of one-ended double-strand DNA breaks (DSBs). This type of DSB break typically arises at collapsed replication forks or at eroded telomeres. BIR initiates by invasion of a broken DNA end into a homologous template followed by initiation of DNA synthesis that can proceed for hundreds of kilobases. This synthesis is drastically different from S-phase replication in that instead of a replication fork, BIR proceeds via a migrating bubble and is associated with conservative inheritance of newly synthesized DNA. This unusual mode of DNA replication is responsible for frequent genetic instabilities associated with BIR, including hyper-mutagenesis, which can lead to the formation of mutation clusters, extensive loss of heterozygosity, chromosomal translocations, copy-number variations and complex genomic rearrangements. In addition to budding yeast experimental systems that were initially employed to investigate eukaryotic BIR, recent studies in different organisms including humans, have provided multiple examples of BIR initiated within different cellular contexts, including collapsed replication fork and telomere maintenance in the absence of telomerase. In addition, significant progress has been made towards understanding microhomology-mediated BIR (MMBIR) that can promote complex chromosomal rearrangements, including those associated with cancer and those leading to a number of neurological disorders in humans.