Break-Induced Replication: The Where, The Why, and The How.
Break-induced replication (BIR) is a pathway that repairs one-ended double-strand breaks (DSBs). For decades, yeast model systems offered the only opportunities to study eukaryotic BIR. These studies described an unusual mode of BIR synthesis that is carried out by a migrating bubble and shows conservative inheritance of newly synthesized DNA, leading to genomic instabilities like those associated with cancer in humans. Yet, evidence of BIR functioning in mammals or during repair of other DNA breaks has been missing. Recent studies have uncovered multiple examples of BIR working in replication restart and repair of eroded telomeres in yeast and mammals, as well as some unexpected findings, including the RAD51 independence of BIR. Strong interest remains in determining the variations in molecular mechanisms that drive and regulate BIR in different genetic backgrounds, across organisms, and particularly in the context of human disease.
['Kramara|J|J|', 'Osia|B|B|', 'Malkova|A|A|']
D000818:Animals D053903:DNA Breaks, Double-Stranded D004260:DNA Repair D004261:DNA Replication D042822:Genomic Instability D006801:Humans D011995:Recombination, Genetic D016615:Telomere
Break-induced replication MMBIR RAD51-independent BIR Rad51-dependent BIR alternative lengthening of telomeres mutation cluster