Anaphase Bridges: Not All Natural Fibers Are Healthy

Abstract

At each round of cell division, the DNA must be correctly duplicated and distributed between the two daughter cells to maintain genome identity. In order to achieve proper chromosome replication and segregation, sister chromatids must be recognized as such and kept together until their separation. This process of cohesion is mainly achieved through proteinaceous linkages of cohesin complexes, which are loaded on the sister chromatids as they are generated during S phase. Cohesion between sister chromatids must be fully removed at anaphase to allow chromosome segregation. Other (non-proteinaceous) sources of cohesion between sister chromatids consist of DNA linkages or sister chromatid intertwines. DNA linkages are a natural consequence of DNA replication, but must be timely resolved before chromosome segregation to avoid the arising of DNA lesions and genome instability, a hallmark of cancer development. As complete resolution of sister chromatid intertwines only occurs during chromosome segregation, it is not clear whether DNA linkages that persist in mitosis are simply an unwanted leftover or whether they have a functional role. In this review, we provide an overview of DNA linkages between sister chromatids, from their origin to their resolution, and we discuss the consequences of a failure in their detection and processing and speculate on their potential role.

Expansion Microscopy Reveals Plasmodium falciparum Blood-Stage Parasites Undergo Anaphase with A Chromatin Bridge in the Absence of Mini-Chromosome Maintenance Complex Binding Protein

“…By visualizing interpolar spindles of MCMBP-deficient parasites at a higher resolution, we were able to update this model. Most prominently, in all interpolar spindles imaged after expansion, there was significant DNA staining inside the bridge region of nuclei connected by interpolar spindles (Figure 4) (Figure S6); this was reminiscent of chromatin bridges that occur during a defective anaphase of other organisms [48,49]. This contrasts with MCMBP HADD parasites grown in the presence of Shld1, where DNA staining was not observed inside this bridge region (Figures 1b and 3a).…”

The Abscission Checkpoint: A Guardian of Chromosomal Stability

“…Origins of DNA Bridges Anaphase DNA bridges, i.e., threads of DNA stretching between the two segregating chromosome masses, can result from unresolved homologous recombination intermediates, incomplete DNA replication, chromosome catenation, or an attempt to segregate dicentric chromosomes that result from telomere-to-telomere fusion (reviewed in [52]). DNA bridges increase in the presence of DNA replication, decatenation or condensation inhibitors, but are also observed even in the absence of exogenous stress, especially at centromeres in mammalian cells [53][54][55].…”

The Last Chance Saloon

“…When fused chromosomes are pulled toward opposite poles during mitosis, chromatin bridges are created (McClintock, 1941). Alternatively, chromatin bridges can also result from persistent intermediates of recombinational repair such as Holliday junctions, from the intertwining of chromosomes, and from chromosomal loci that have not been replicated by the time cells reach the metaphase-anaphase transition (Finardi et al, 2020; Figure 1A). Regions susceptible to under-replication include centromeres, telomeres and common fragile sites, all containing sequences inherently difficult to replicate (Mankouri et al, 2013).…”