DNA RENATURATION ACTIVITY OF THE SMC COMPLEX IMPLICATED IN CHROMOSOMECONDENSATION

Chromosome condensation occurs in mitosis before the separation of sis ter chromatids, and requires DNA topoisomerase II (refs 1, 2) and a gr oup of proteins called SMCs3-5. The resulting condensed chromosomes in metaphase have a complex hierarchical structure(6,7). SMCs, the compo nents of condensed chromosomes, are also required for the separation o f sister chromatids and gene dosage compensation, and are found in a r ange of organisms from yeasts to mammals(8-13). However, the mechanism s by which the SMCs contribute to chromosome condensation are unknown. We have studied chromosomes in fission-yeast SMC mutants cut3-477 and cut14-208 (ref. 9), which remain largely non-condensed during mitosis at the restrictive temperature (36 degrees C)(9). To test their role in DNA condensation, we isolated the proteins Cut3 and Cut14 as an oli gomeric complex, and tested their interactions with isolated DNA. The complex efficiently promoted the DNA renaturation reactions (the windi ng up of single-strand DNAs into double helical DNA) as much as simila r to 70-fold more efficiently than RecA(14), which is a bacterial prot ein with similar activity. The activity of the mutant complex was heat sensitive. As DNA winding by renaturation is a potential cause of sup ercoiling, the SMC complex may be implicated in promoting the higher-o rder DNA coiling found in condensed chromosomes.