The mortal strand hypothesis: non-random chromosome inheritance and the biased segregation of damaged DNA.

If a eukaryotic cell is to reproduce, it must duplicate its genetic information in the form of DNA, and faithfully segregate that information during a complex process of cell division. During this division process, the resulting cells inherit one, and only one, copy of each chromosome. Over thirty years ago, it was predicted that the segregation of sister chromosomes could occur non-randomly, such that a daughter cell would preferentially inherit one of the two sister chromosomes according to some characteristic of that chromosome's template DNA strand. Although this prediction has been confirmed in studies of various cell-types, we know little of both the mechanism by which the asymmetric inheritance occurs and the significance it has to cells. In this essay, we propose a new model of non-random chromosome segregation-the mortal strand hypothesis-and discuss tests of the model that will provide insight into the molecular choreography of this intriguing phenomenon. Published by Elsevier Ltd.