The structure of human S-phase chromosome fibres

Recent in situ hybridization studies suggested that within the range of 0.1-1.0 Mb, human interphase chromosomes follow a random walk model (i.e. they behave as flexible polymers without major constraints). However, chromosome structure may differ in the G1, S, and G2 phases, and phase-specific constraints may be masked if the chromosome analysis does not discriminate between the phases. Therefore, using confocal microscopy, we examined the structure of S-phase chromosomes labelled with 5-iododeoxyuridine after prolonged treatment with 5-fluorodeoxyuridine. In the S-phase, labelled 0.32 mu chromosome fibres mostly appear as semi-circles with an average diameter of 0.83 +/- 0.03 mu. These semi-circles are joined together to form different 3D structures, and two semicircles frequently adopt s- or omega-like conformations involving about 2.5 mu of the chromosome contour length (L). Morphometric analysis of the S-phase fibres suggests that our data fit both the random flexible polymer model and also a model in which two constrained semi-circles are attached to each other by a flexible joint, thus eliminating constraints at long distances (L more than 2 mu).