Nucleolar integrity during interphase supports faithful Cdk1 activation and mitotic entry

Abstract

The maintenance of nucleolar integrity during interphase is essential for proper cell cycle progression to mitosis.

Paired Box 9 (PAX9), the RNA polymerase II transcription factor, regulates human ribosome biogenesis and craniofacial development

“…As disruptions in ribosome biogenesis result in interruptions in the cell cycle [43][44][45][46][47][48], we also examined the extent to which PAX9 depletion changed the distribution of MCF10A cells within the cell cycle using flow cytometry ( [49]. In all, these assays allowed us to conclude that PAX9 regulates human ribosome biogenesis.…”

Identification of a novel nucleolar protein complex required for mitotic chromosome segregation through centromeric accumulation of Aurora B

“…Fluorescence-activated cell sorting (FACS) analysis showed that the mitotic index was increased by more than twofold in NOL11-depleted cells compared to that observed in control cells (Figure 4B ). In contrast, TIF-IA depletion, which also caused nucleolar disruption and delayed mitotic entry similarly to NOL11 depletion ( 23 ), had a limited effect on the mitotic index (Figure 4B ). Mitotic cells depleted of NOL11 appeared to spend a longer time progressing from prophase to metaphase as indicated by their increased population (Figure 4C ).…”

“…We previously found that NOL11 depletion caused precocious nucleolar disruption during interphase, which in turn suppressed the activation of Cdk1 and delayed mitotic entry ( 23 ). It has been known that treating cells with low-dose Cdk1 inhibitor RO-3306 causes several mitotic chromosomal defects and polyploidy ( 53 , 54 ).…”

“…Therefore, it was formally possible that an insufficient activity of Cdk1 underlies the mitotic phenotypes of NWC depletion, including metaphase arrest, chromosome misalignment, concentration defect of Aurora B at centromeres, defect in sister chromatid cohesion, and delocalisation of several centromere/kinetochore proteins (Figure 4C and D , 5C, and 6; Supplementary Figures S6, S7, S8 and S12 ). However, it is unlikely that this is the case for NOL11 depletion, as the level of the Cdk1 activity eventually reached the level attained in unperturbed mitosis, indicated by Cdk1-dependent MPM2 phosphoepitope ( 23 ). Depletion of TIF-IA, another protein involved in rRNA transcription at nucleoli, also caused nucleolar disruption in interphase nuclei and delayed Cdk1 activation ( 23 ), supporting the idea that delayed mitotic entry is a common consequence after nucleolar disruption.…”

“…It was previously reported that a nucleolar factor called nucleolar protein 11 (NOL11), which is essential for optimal pre-rRNA transcription and processing ( 22 ), is required for nucleolar integrity during interphase, which relates to the timely activation of cyclin-dependent kinase 1 (Cdk1) and mitotic entry ( 23 ). There seemed more to NOL11 than controlling mitotic entry, as NOL11 depletion affected mitotic transitions reflected by an obvious increase of the mitotic index ( 23 ). In the present study, we found that NOL11 forms a protein complex with two characteristic tryptophan-aspartic acid (WD) repeat proteins named WD-repeat protein 43 (WDR43) and Cirhin.…”