Chromatin bridges: stochastic breakage or regulated resolution?

Chromatin bridges mostly arise from dicentric chromosomes resulting from chromosome end-to-end fusions due to telomere crisis, erroneous DNA repair, and neocentromere formation. Accumulation of interchromosomal linkages also leads to chromatin bridges.Actomyosin contractile forces can break chromatin bridges after they have been stretched to extend.TREX1 is a 3′–5′ exonuclease that has been implicated in processing stretched chromatin bridges after nuclear envelope rupture. TREX1 degrades bridge DNA to generate extensive single-stranded DNA (ssDNA) along the bridges.ANKLE1 is a midbody-tethered endonuclease that cleaves DNA bridges to avoid catastrophic breakage of bridges by actomyosin-mediated mechanical forces.The breakage of chromatin bridges induces micronuclei, the DNA of which is prone to damage. Damaged micronuclei promote chromothripsis. Genetic material is organized in the form of chromosomes, which need to be segregated accurately into two daughter cells in each cell cycle. However, chromosome fusion or the presence of unresolved interchromosomal linkages lead to the formation of chromatin bridges, which can induce DNA lesions and genome instability. Persistent chromatin bridges are trapped in the cleavage furrow and are broken at or after abscission, the final step of cytokinesis. In this review, we focus on recent progress in understanding the mechanism of bridge breakage and resolution. We discuss the molecular machinery and enzymes that have been implicated in the breakage and processing of bridge DNA. In addition, we outline both the immediate outcomes and genomic consequences induced by bridge breakage. Genetic material is organized in the form of chromosomes, which need to be segregated accurately into two daughter cells in each cell cycle. However, chromosome fusion or the presence of unresolved interchromosomal linkages lead to the formation of chromatin bridges, which can induce DNA lesions and genome instability. Persistent chromatin bridges are trapped in the cleavage furrow and are broken at or after abscission, the final step of cytokinesis. In this review, we focus on recent progress in understanding the mechanism of bridge breakage and resolution. We discuss the molecular machinery and enzymes that have been implicated in the breakage and processing of bridge DNA. In addition, we outline both the immediate outcomes and genomic consequences induced by bridge breakage.