Biased DNA Segregation


Biased chromatid segregation refers to the nonrandom distribution of chromatids in mitotic cells so that specific daughters inherit specific chromosomes or deoxyribonucleic acid (DNA) strands. This unusual behaviour has been documented primarily in the context of differentiation, when one cell divides to produce two daughter cells with distinct fates. When cells divide asymmetrically to produce such daughters, it has been noted that the DNA in these different daughter cells is dissimilar. Two controversial hypotheses to account for such data have been envisioned thus far: one in which stem cells retain all chromosomes carrying ancestral DNA strands, and one in which precursors segregate one or more, epigenetically dissimilar, strands nonrandomly. Several cases of biased DNA segregation are presented, and the implications of this theory are discussed with a view to general biological issues, the proximate mechanisms underlying these phenomena and the ultimate reasons these might occur.

Key Concepts:

  • The biased segregation of DNA might function to specify the fate of cells.

  • It has been proposed that biased DNA segregation reduces DNA mutation load in the cell that retains ancestral, or original, DNA strands.

  • Stem cell self‐renewal and multipotency, which are accounted for by asymmetric cell division, are also proposed to be an outcome of biased DNA segregation.

Keywords: differentiation; asymmetric division; stem cells; epigenetics; mutation; cancer

Figure 1.

Two models of biased DNA segregation. (a) Depicts biased DNA segregation. A hypothetical precursor (which might be a stem cell or simply a precursor present during development) containing epigenetically distinct strands (shown in green and red). When segregated, these strands determine daughter cell fate as a consequence of the configuration of genes transcribed from those strands. Even though each daughter contains strands that are genetic copies, the epigenetic structure in the green versus red strands is different. These green and red strands are hypothesised to be nonrandomly segregated into specific cells in order to determine their fate. (b) Depicts ancestral strand retention as predicted by the immortal strand hypothesis. A stem cell contains ancestral strands (red) specified at some point during development to be retained in that cell if it divides asymmetrically. Following asymmetric division, these red strands are retained by the stem cell daughter, but not the nonstem cell daughter destined to differentiate. The retention of the red strands is hypothesised to minimise mutation load as the sequence in them is not recopied during the many S phases a stem cell undergoes throughout the lifetime of an organism. As above, it is also hypothesised that structural differences in the red strands could also play a role in differentiation.



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Further Reading

Tajbakhsh S and Gonzalez C (2009) Biased segregation of DNA and centrosomes: moving together or drifting apart? Nature Reviews. Molecular Cell Biology 10: 804–810.

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Karpowicz, Phillip(Sep 2010) Biased DNA Segregation. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0022543]