The decatenation checkpoint

Abstract

The decatenation checkpoint delays entry into mitosis until the chromosomes have been disentangled. Deficiency in or bypass of the decatenation checkpoint can cause chromosome breakage and nondisjunction during mitosis, which results in aneuploidy and chromosome rearrangements in the daughter cells. A deficiency in the decatenation checkpoint has been reported in lung and bladder cancer cell lines and may contribute to the accumulation of chromosome aberrations that commonly occur during tumour progression. A checkpoint deficiency has also been documented in cultured stem and progenitor cells, and cancer stem cells are likely to be derived from stem and progenitor cells that lack an effective decatenation checkpoint. An inefficient decatenation checkpoint is likely to be a source of the chromosome aberrations that are common features of most tumours, but an inefficient decatenation checkpoint in cancer stem cells could also provide a potential target for chemotherapy.

Figure 1

(A) Mitosis in the presence of entangled chromosomes leads to aneuploidy. The decatenation checkpoint guards against nondisjunction and chromosome breakage that occur when the cell enters mitosis before the chromosomes have been sufficiently decatenated by Topo II. (B) Working model of decatenation checkpoint signalling. (C) Checkpoint deficiency in cancer cells could result in additional chromosome imbalances that increase tumour malignancy (top). The presence of additional chromosome aberrations is represented by darker colour of the nucleus. Decatenation checkpoint deficiency is an inherent feature of stem and progenitor cells and may lead to the formation of cancer stem cells (bottom). Chemotherapy that targets the decatenation checkpoint may efficiently target cancer cells and CSCs.