Condensin targets and reduces unwound DNA structures associated with transcription in mitotic chromosome condensation

Abstract

Chromosome condensation is a hallmark of mitosis in eukaryotes and is a prerequisite for faithful segregation of genetic material to daughter cells. Here we show that condensin, which is essential for assembling condensed chromosomes, helps to preclude the detrimental effects of gene transcription on mitotic condensation. ChIP-seq profiling reveals that the fission yeast condensin preferentially binds to active protein-coding genes in a transcription-dependent manner during mitosis. Pharmacological and genetic attenuation of transcription largely rescue bulk chromosome segregation defects observed in condensin mutants. We also demonstrate that condensin is associated with and reduces unwound DNA segments generated by transcription, providing a direct link between an in vitro activity of condensin and its in vivo function. The human condensin isoform condensin I also binds to unwound DNA regions at the transcription start sites of active genes, implying that our findings uncover a fundamental feature of condensin complexes.

Structural basis ofHEAT‐kleisin interactions in the human condensin I subcomplex

“…Although we have been unable to obtain any crystals with a longer stretch hCAP‐H, our DNA binding assay clearly showed that hCAP‐H is indeed required to make DNA‐binding surface together with hCAP‐G. It remains unknown whether the ability of the hCAP‐G‐H subcomplex to interact with ssDNA, which was not observed for its yeast counterpart, may be related to the previously proposed function of condensin I in transcribing regions to regenerate dsDNA . In the future, it will be important to further clarify the similarities and detailed differences in the structure and function of this fundamental chromosome organizing machinery among different eukaryotic species.…”

Condensin-mediated chromosome organization in fission yeast

“…Mitotic defects caused by the condensin mutation are suppressed by inhibiting Pol III and Pol II transcription (Iwasaki et al 2010; Sutani et al 2015). Note that this condensin mutation is temperature-sensitive and partially impairs condensin activity.…”

“…Our study suggests that the kleisin subunit of the human condensin I complex, hCAP-H (Cnd2 cognate), interacts with human TBP (Iwasaki et al 2015a). As in fission yeast cells, condensin is enriched at highly transcribed genes in higher eukaryotes (Kim et al 2013; Sutani et al 2015). It has recently been shown that condensin mediates gene looping and activation in human cells, and that condensin mutations are significantly accumulated in various cancer types (Li et al 2015; Leiserson et al 2015).…”

DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments

“…Condensin is recruited to highly transcribed genes, probably by targeting unwound DNA segments [55]. The RPA mutation that suppresses the cohesion defect was originally identified as suppressor of a temperature-sensitive condensin mutant in fission yeast [56].…”