Cohesion, but not too close

After DNA replication in eukaryotes, the daughter chromatids remain connected throughout G2 and mitosis until they separate in anaphase. In budding yeast, the chromosomal cohesin complex has been shown to bind the chromatids together tightly at multiple points approximately every 10 kb along their entire length. What happens in human cells? Are sister chromatids also bound along their entire length from S-phase to the onset of anaphase? The two homologues of human chromosome 6 were visualised together with the major histocompatibility complex (MHC) class II region at band 6p21 by fluorescence in situ hybridisation in the human fibroblast cell line MRC5 (see Volpi et al., J Cell Sci 2000, 113:1565-1576). As expected, a single signal is seen at this locus in G0 and G1, which duplicates to form a doublet in S-phase. Surprisingly, however, in many cells the daughter signals are observed some distance apart. In metaphase, signals join again on adjacent sister chromatids (from top to bottom in the left-hand panel; chromosome 6 in green, MHC class II in red). The unexpectedly distant configuration in G2 was also found for the MHC class I and III regions, and for a gene-poor region from band 6p24 (from top to bottom in the righthand panel). These observations indicate that sister chromatids, at least in human cells, are not always closely aligned in the period between DNA replication and mitosis, thus challenging currently held views on sister chromatid cohesion. Address: Imperial Cancer Research Fund,