Differential Requirements for the CENP-O Complex Reveal Parallel PLK1 Kinetochore Recruitment Pathways

Similar to other core biological processes, the vast majority of cell division components are essential for viability across human cell lines. However, recent genome‐wide screens have identified a number of proteins that exhibit cell line‐specific essentiality. Defining the behaviors of these proteins is critical to our understanding of complex biological processes. Here, we harness differential essentiality to reveal the contributions of the 4‐subunit centromere‐localized CENP‐O complex, whose precise function has been difficult to define. Our results support a model in which the CENP‐O complex and BUB1 act in parallel pathways to recruit a threshold level of PLK1 to mitotic kinetochores, ensuring accurate chromosome segregation. We demonstrate that targeted changes to either pathway sensitizes cells to the loss of the other component, resulting in cell‐state dependent requirements. This approach also highlights the advantage of comparing phenotypes across diverse cell lines to define critical functional contributions and behaviors that could be exploited for the targeted treatment of disease.

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Differential Requirements for the CENP-O Complex Reveal Parallel PLK1 Kinetochore Recruitment Pathways

10.1101/2020.11.30.404327 ◽

2020 ◽

Author(s):

Alexandra L. Nguyen ◽

Marie Diane Fadel ◽

Iain M. Cheeseman

Keyword(s):

Cell Division ◽

Cell Lines ◽

Chromosome Segregation ◽

Human Cell ◽

Threshold Level ◽

The Other ◽

Biological Processes ◽

Human Cell Lines ◽

State Dependent ◽

Genome Wide

AbstractSimilar to other core biological processes, the vast majority of cell division components are essential for viability across human cell lines. However, genome-wide screens have identified a number of proteins that exhibit cell line-specific essentiality. Defining the behaviors of these proteins is critical to our understanding of complex biological processes. Here, we harness differential essentiality to reveal the contributions of the 4-subunit centromere-localized CENP-O complex, whose precise function has been difficult to define. Our results support a model in which the CENP-O complex and BUB1 act in parallel pathways to recruit a threshold level of PLK1 to mitotic kinetochores, ensuring accurate chromosome segregation. We demonstrate that targeted changes to either pathway sensitizes cells to the loss of the other component, resulting in cell-state dependent requirements. This approach also highlights the advantage of comparing phenotypes across diverse cell lines to define critical functional contributions and behaviors that could be exploited for the targeted treatment of disease.

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Genome-wide nucleosome occupancy and DNA methylation profiling of four human cell lines

Genomics Data ◽

10.1016/j.gdata.2014.11.012 ◽

2015 ◽

Vol 3 ◽

pp. 94-96 ◽

Cited By ~ 8

Author(s):

Aaron L. Statham ◽

Phillippa C. Taberlay ◽

Theresa K. Kelly ◽

Peter A. Jones ◽

Susan J. Clark

Keyword(s):

Dna Methylation ◽

Cell Lines ◽

Human Cell ◽

Nucleosome Occupancy ◽

Human Cell Lines ◽

Genome Wide ◽

Dna Methylation Profiling ◽

Methylation Profiling

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Screening for 15 pathogenic viruses in human cell lines registered at the JCRB Cell Bank: characterization of in vitro human cells by viral infection

Royal Society Open Science ◽

10.1098/rsos.172472 ◽

2018 ◽

Vol 5 (5) ◽

pp. 172472 ◽

Cited By ~ 2

Author(s):

Setsuko Shioda ◽

Fumio Kasai ◽

Ken Watanabe ◽

Kohei Kawakami ◽

Azusa Ohtani ◽

...

Keyword(s):

Viral Infection ◽

Cell Line ◽

Cell Lines ◽

Human Cell ◽

The Other ◽

Pcr Analysis ◽

Human Cell Lines ◽

Cell Bank

Human cell lines have been used in a variety of research fields as an in vitro model. These cells are all derived from human tissue samples, thus there is a possibility of virus infection. Virus tests are routinely performed in clinical practice, but are limited in cell lines. In this study, we investigated 15 kinds of viruses in 844 human cell lines registered at the Japanese Collection of Research Bioresources (JCRB) Cell Bank. Our real-time PCR analysis revealed that six viruses, EBV, HTLV-1, HBV, B19V, HHV-6 and HHV-7, were detected in 43 cell lines. Of them, 20 cell lines were transformed by intentional infection in vitro with EBV or HTLV-1. Viruses in the other 23 cell lines and one EBV transformed cell line are derived from an in vivo infection, including five de novo identifications of EBV, B19V or HHV-7 carriers. Among them, 17 cell lines were established from patients diagnosed with virus-associated diseases. However, the other seven cell lines originated from in vivo cells unrelated to disease or cellular tropism. Our approach to screen for a set of 15 viruses in each cell line has worked efficiently to identify these rare cases. Virus tests in cell lines contribute not only to safety assessments but also to investigation of in vivo viral infection which can be a characteristic feature of cell lines.

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Genome-wide DNA methylation analysis in cohesin mutant human cell lines

Nucleic Acids Research ◽

10.1093/nar/gkq346 ◽

2010 ◽

Vol 38 (17) ◽

pp. 5657-5671 ◽

Cited By ~ 14

Author(s):

Jinglan Liu ◽

Zhe Zhang ◽

Masashige Bando ◽

Takehiko Itoh ◽

Matthew A. Deardorff ◽

...

Keyword(s):

Dna Methylation ◽

Cell Lines ◽

Human Cell ◽

Human Cell Lines ◽

Methylation Analysis ◽

Genome Wide ◽

Dna Methylation Analysis

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2′O-Ribose Methylation of Ribosomal RNAs: Natural Diversity in Living Organisms, Biological Processes, and Diseases

Cells ◽

10.3390/cells10081948 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1948

Author(s):

Mariam Jaafar ◽

Hermes Paraqindes ◽

Mathieu Gabut ◽

Jean-Jacques Diaz ◽

Virginie Marcel ◽

...

Keyword(s):

Chemical Modification ◽

Single Cell ◽

Cell Line ◽

Cell Lines ◽

Human Cell ◽

Biological Processes ◽

Human Cell Lines ◽

Natural Diversity ◽

Living Organisms ◽

Line Organ

Recent findings suggest that ribosomes, the translational machineries, can display a distinct composition depending on physio-pathological contexts. Thanks to outstanding technological breakthroughs, many studies have reported that variations of rRNA modifications, and more particularly the most abundant rRNA chemical modification, the rRNA 2′O-ribose methylation (2′Ome), intrinsically occur in many organisms. In the last 5 years, accumulating reports have illustrated that rRNA 2′Ome varies in human cell lines but also in living organisms (yeast, plant, zebrafish, mouse, human) during development and diseases. These rRNA 2′Ome variations occur either within a single cell line, organ, or patient’s sample (i.e., intra-variability) or between at least two biological conditions (i.e., inter-variability). Thus, the ribosomes can tolerate the absence of 2′Ome at some specific positions. These observations question whether variations in rRNA 2′Ome could provide ribosomes with particular translational regulatory activities and functional specializations. Here, we compile recent studies supporting the heterogeneity of ribosome composition at rRNA 2′Ome level and provide an overview of the natural diversity in rRNA 2′Ome that has been reported up to now throughout the kingdom of life. Moreover, we discuss the little evidence that suggests that variations of rRNA 2′Ome can effectively impact the ribosome activity and contribute to the etiology of some human diseases.

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Genome wide mapping of UBF binding-sites in mouse and human cell lines

Genomics Data ◽

10.1016/j.gdata.2014.12.005 ◽

2015 ◽

Vol 3 ◽

pp. 103-105 ◽

Cited By ~ 5

Author(s):

Jeannine Diesch ◽

Ross D. Hannan ◽

Elaine Sanij

Keyword(s):

Cell Lines ◽

Human Cell ◽

Binding Sites ◽

Human Cell Lines ◽

Genome Wide

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Genome-wide analysis of H3K36me3 and its regulations to cancer-related genes expression in human cell lines

Biosystems ◽

10.1016/j.biosystems.2018.07.004 ◽

2018 ◽

Vol 171 ◽

pp. 59-65 ◽

Cited By ~ 1

Author(s):

Lu-Qiang Zhang ◽

Qian-Zhong Li ◽

Wen Jin ◽

Yongchun Zuo ◽

Shu-Chun Guo

Keyword(s):

Cell Lines ◽

Human Cell ◽

Human Cell Lines ◽

Genome Wide Analysis ◽

Genome Wide ◽

Genes Expression

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Effect of Nitric Oxide on Poliovirus Infection of Two Human Cell Lines

Journal of Virology ◽

10.1128/jvi.72.3.2538-2540.1998 ◽

1998 ◽

Vol 72 (3) ◽

pp. 2538-2540 ◽

Cited By ~ 19

Author(s):

José A. López-Guerrero ◽

Luis Carrasco

Keyword(s):

Nitric Oxide ◽

Cell Lines ◽

Human Cell ◽

The Other ◽

Nitric Oxide Donor ◽

Human Cell Lines ◽

Poliovirus Infection ◽

Other Hand

ABSTRACT The role of nitric oxide after poliovirus infection of the human HeLa (carcinoma) and U937 (promonocytic) cell lines has been analyzed. Both types of cells produced detectable levels of nitric oxide after poliovirus infection. However, this production was not sufficient to limit viral productivity. On the other hand, pretreatment with the nitric oxide donor glycerine trinitrate lengthened the course of poliovirus infection.

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