Abstract
Accurate duplication and transmission of identical genetic information into offspring cells lies at the heart of a cell division cycle. During the last stage of cellular division, namely mitosis, the fully replicated DNA molecules are condensed into X-shaped chromosomes, followed by a chromosome separation process called sister chromatid disjunction. This process allows for the equal partition of genetic material into two newly born daughter cells. However, emerging evidence has shown that faithful chromosome segregation is challenged by the presence of persistent DNA intertwining structures generated during DNA replication and repair, which manifest as so-called ultra-fine DNA bridges (UFBs) during anaphase. Undoubtedly, failure to disentangle DNA linkages poses a severe threat to mitosis and genome integrity. This review will summarize the possible causes of DNA bridges, particularly sister DNA inter-linkage structures, in an attempt to explain how they may be processed and how they influence faithful chromosome segregation and the maintenance of genome stability.
Highlights
Accurate duplication and transmission of identical genetic information into offspring cells lies at the heart of a cell division cycle
In addition to replication intermediate-induced ultra-fine DNA bridges (UFBs), recently, two groups have reported the identification of HR-induced UFBs (HR-UFBs) in human cells, showing that these UFBs are not associated with FANCD2 protein and their formation relies on homologous recombination pathway activation
RIF1 may associate to UFBs via other Plk1-interacting checkpoint helicase (PICH) binding partners that are independent of Bloom’s syndrome helicase (BLM), such as TOP3A and RMI1/2
Summary
Chromosome mis-segregation is widely implicated in genomic instability diseases such as cancer [1]. It is referred to as the appearance of incompletely separated chromosomes that manifest as bulky DNA bridges that remain connected, or alternatively, as the appearance of chromatin lagging between the daughter nuclear masses during anaphase. 1930, Barbara McClintock proposed that anaphase bridges drive chromosome instability through a so-called breakage-fusion-bridge cycle mechanism [2,3] She suggested that if inappropriate repair of DNA breaks occurs between chromatid arms, or dysfunctional telomeres of different chromosomes, this can lead to chromosomal fusion and the formation of dicentric chromosomes, which comprise two centromeres. It provides a representation of how anaphase bridges and lagging chromosomes are generated, as well as, their pathological consequences. Spindle attachment errors include microtubule connection on single kinetochore (monotelic), attachment of two sister kinetochores from the same spindle pole (syntelic) and attachment of a single kinetochore to microtubules emanating from two spindle poles (merotelic)
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