Invadolysin acts genetically via the SAGA complex to modulate chromosome structure.
Bottom Line: Over-expression of the Bre1 ubiquitin ligase phenocopies the effects of mutating either the invadolysin or nonstop genes.We further suggest that the mislocalization of ubH2B to the cytoplasm has additional consequences on downstream components essential for chromosome behaviour.We therefore propose that invadolysin plays a crucial role in chromosome organization via its interaction with the SAGA complex.
Affiliation: University of Edinburgh, Queen's Medical Research Institute, University/BHF Centre for Cardiovascular Science, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.Show MeSH
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Mentions: Based on our results, we propose the model in Figure 8 for the role of invadolysin in higher-order chromosome structure. Invadolysin may work to balance the dBre1 [ubiquitinating] and nonstop [deubiquitinating] activities to regulate histone ubiquitination and ensuing chromosomal architecture. When ubH2B accumulates in the cytoplasm or on mitotic chromosomes, chromosome structure is affected, such that chromosomes appear hypercondensed in length, yet fuzzy in periphery. Cytoplasmic ubH2B accumulation may also result in changes in transcription via the accumulation of H3K4me3. We have not yet determined whether the genetic interaction described herein is also mirrored by direct physical interaction between invadolysin and SAGA complex subunits.
Affiliation: University of Edinburgh, Queen's Medical Research Institute, University/BHF Centre for Cardiovascular Science, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.