New Insights into Mitotic Chromosome Condensation: A Role for the Prolyl Isomerase Pin1

The advent of genome-wide RNA interference (RNAi)–based screens puts us in the position to identify genes for all functions human cells carry out. However, for many functions, assay complexity and cost make genome-scale knockdown experiments impossible. Methods to predict genes required for cell functions are therefore needed to focus RNAi screens from the whole genome on the most likely candidates. Although different bioinformatics tools for gene function prediction exist, they lack experimental validation and are therefore rarely used by experimentalists. To address this, we developed an effective computational gene selection strategy that represents public data about genes as graphs and then analyzes these graphs using kernels on graph nodes to predict functional relationships. To demonstrate its performance, we predicted human genes required for a poorly understood cellular function—mitotic chromosome condensation—and experimentally validated the top 100 candidates with a focused RNAi screen by automated microscopy. Quantitative analysis of the images demonstrated that the candidates were indeed strongly enriched in condensation genes, including the discovery of several new factors. By combining bioinformatics prediction with experimental validation, our study shows that kernels on graph nodes are powerful tools to integrate public biological data and predict genes involved in cellular functions of interest.

Download Full-text

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

Nature Communications ◽

10.1038/ncomms8815 ◽

2015 ◽

Vol 6 (1) ◽

Cited By ~ 57

Author(s):

Takashi Sutani ◽

Toyonori Sakata ◽

Ryuichiro Nakato ◽

Koji Masuda ◽

Mai Ishibashi ◽

...

Keyword(s):

Mitotic Chromosome ◽

Chromosome Condensation ◽

Dna Structures ◽

Mitotic Chromosome Condensation

Download Full-text

Mitotic chromosome condensation requires phosphorylation of the centromeric protein KNL-2 in C. elegans

10.1101/2021.07.01.450752 ◽

2021 ◽

Author(s):

Joanna M Wenda ◽

Reinier F Prosée ◽

Caroline Gabus ◽

Florian A Steiner

Keyword(s):

Chromosome Segregation ◽

Mitotic Chromosome ◽

Chromosome Condensation ◽

Embryonic Lethality ◽

Phosphorylation Sites ◽

C Elegans ◽

Microtubule Attachment ◽

Centromeric Protein ◽

Mitotic Chromosome Condensation

Centromeres are chromosomal regions that serve as sites for kinetochore formation and microtubule attachment, processes that are essential for chromosome segregation during mitosis. Centromeres are almost universally defined by the histone variant CENP-A. In the holocentric nematode C. elegans, CENP-A deposition depends on the loading factor KNL-2. Depletion of either CENP-A or KNL-2 results in defects in centromere maintenance, chromosome condensation and kinetochore formation, leading to chromosome segregation failure. Here, we show that KNL-2 is phosphorylated by CDK-1, and that mutation of three C-terminal phosphorylation sites causes chromosome segregation defects and an increase in embryonic lethality. In strains expressing phosphodeficient KNL-2, CENP-A and kinetochore proteins are properly localised, indicating that the role of KNL-2 in centromere maintenance is not affected. Instead, the mutant embryos exhibit reduced mitotic levels of condensin II on chromosomes and significant chromosome condensation impairment. Our findings separate the functions of KNL-2 in CENP-A loading and chromosome condensation and demonstrate that KNL-2 phosphorylation regulates the cooperation between centromeric regions and the condensation machinery in C. elegans.

Download Full-text

Novel insights into mitotic chromosome condensation

F1000Research ◽

10.12688/f1000research.8727.1 ◽

2016 ◽

Vol 5 ◽

pp. 1807 ◽

Cited By ~ 16

Author(s):

Ewa Piskadlo ◽

Raquel A. Oliveira

Keyword(s):

Cell Division ◽

Topoisomerase Ii ◽

Mitotic Chromosome ◽

Nuclear Division ◽

Chromosome Condensation ◽

Cell Division Cycle ◽

Chromosome Organization ◽

Condensation Process ◽

Successful Completion ◽

Mitotic Chromosome Condensation

The fidelity of mitosis is essential for life, and successful completion of this process relies on drastic changes in chromosome organization at the onset of nuclear division. The mechanisms that govern chromosome compaction at every cell division cycle are still far from full comprehension, yet recent studies provide novel insights into this problem, challenging classical views on mitotic chromosome assembly. Here, we briefly introduce various models for chromosome assembly and known factors involved in the condensation process (e.g. condensin complexes and topoisomerase II). We will then focus on a few selected studies that have recently brought novel insights into the mysterious way chromosomes are condensed during nuclear division.

Download Full-text