Mechanisms behind Topoisomerase II SUMOylation in chromosome segregation

Yoshida, Makoto M; Azuma, Yoshiaki

doi:10.1080/15384101.2016.1216928

Cited by 12 publications

(13 citation statements)

References 7 publications

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“…Other genes with protein-coding SNCs ( NEK6, STARD9/KIF16A and CDK5RAP2 ) turn out to be implicated in the regulation of spindle pole assembly as well 62–64 . Among the 15 fixed protein-coding changes identified here but absent from previous analyses 1,20 , some might have also contributed to complex modifications of pathways in cell division, like AHR 65 or DNHD1 66 (Supplementary Information 1), as well as other genes with HHMCs, like CHEK1 67 or the gene encoding for the protein TOP2A 68 , which shows the largest number of interactions with other HHMC-carrying proteins, suggesting a function as interaction hub in the cell division complex (Supplementary Information 1). Taken together, these changes suggest that the cell cycle machinery might have been modified in a specific way in humans compared to other hominins.…”

Section: Discussionmentioning

confidence: 69%

A catalog of single nucleotide changes distinguishing modern humans from archaic hominins

Kuhlwilm

Boeckx

2019

Sci Rep

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Throughout the past decade, studying ancient genomes has provided unique insights into human prehistory, and differences between modern humans and other branches like Neanderthals can enrich our understanding of the molecular basis of unique modern human traits. Modern human variation and the interactions between different hominin lineages are now well studied, making it reasonable to go beyond fixed genetic changes and explore changes that are observed at high frequency in present-day humans. Here, we identify 571 genes with non-synonymous changes at high frequency. We suggest that molecular mechanisms in cell division and networks affecting cellular features of neurons were prominently modified by these changes. Complex phenotypes in brain growth trajectory and cognitive traits are likely influenced by these networks and other non-coding changes presented here. We propose that at least some of these changes contributed to uniquely human traits, and should be prioritized for experimental validation.

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Section: Discussionmentioning

confidence: 69%

A catalog of single nucleotide changes distinguishing modern humans from archaic hominins

Kuhlwilm

Boeckx

2019

Sci Rep

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“…Six genes are involved in spindle function and chromosome segregation, which includes KIF11 ( Rapley et al, 2008 ), NUP62 ( Hashizume et al, 2013 ), SPDL1 ( Gassmann et al, 2008 ), and three core chromosomal passenger complex components INCENP , AURKB , and CDCA8 ( Terada, 2001 ; Carmena et al, 2012 ). Three genes function in DNA damage and repair, namely TICRR ( Sansam et al, 2010 ; Yu et al, 2019 ), TOP2A ( Bower et al, 2010 ; Yoshida and Azuma, 2016 ), and RAD51 ( Yoon et al, 2014 ; Sullivan and Bernstein, 2018 ), while the remaining four play roles in histone synthesis ( CASP8AP2 ; Sokolova et al, 2017 ), DNA maintenance ( DNA2 ; Duxin et al, 2009 ; Pawłowska et al, 2017 ), and cell cycle regulation ( SKA1 ; Sivakumar et al, 2014 , 2016 ; and FBXO5 ; Verschuren et al, 2007 ; Machida and Dutta, 2007 ; Data S3 ). Some of these functions might directly explain the larger nuclei phenotype after knockdown.…”

Section: Resultsmentioning

confidence: 99%

High-content imaging-based pooled CRISPR screens in mammalian cells

Yan

Stuurman

Ribeiro

et al. 2021

Journal of Cell Biology

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CRISPR (clustered regularly interspaced short palindromic repeats)-based gene inactivation provides a powerful means for linking genes to particular cellular phenotypes. CRISPR-based screening typically uses large genomic pools of single guide RNAs (sgRNAs). However, this approach is limited to phenotypes that can be enriched by chemical selection or FACS sorting. Here, we developed a microscopy-based approach, which we name optical enrichment, to select cells displaying a particular CRISPR-induced phenotype by automated imaging-based computation, mark them by photoactivation of an expressed photoactivatable fluorescent protein, and then isolate the fluorescent cells using fluorescence-activated cell sorting (FACS). A plugin was developed for the open source software μManager to automate the phenotypic identification and photoactivation of cells, allowing ∼1.5 million individual cells to be screened in 8 h. We used this approach to screen 6,092 sgRNAs targeting 544 genes for their effects on nuclear size regulation and identified 14 bona fide hits. These results present a scalable approach to facilitate imaging-based pooled CRISPR screens.

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“…implicated in the regulation of spindle pole assembly as well(O'Regan and Fry 2009;Torres et al 2017). Among the 15 fixed protein-coding changes identified here but absent from previous analyses(Pääbo 2014;Prüfer et al 2014), some might have also contributed to complex modifications of pathways in cell division, like AHR(Puga et al 2002) or DNHD1 (Bader et al2011) (SupplementaryInformation 1), as well as other genes with HHMCs, like CHEK1(Zachos et al 2017) or the gene encoding for the protein TOP2A(Yoshida and Azuma 2016), which shows the largest number of interactions with other HHMC-carrying proteins, suggesting a function as interaction hub in the cell division complex(Supplementary Information 1). Taken together, these changes suggest that the cell cycle machinery might have been modified in a specific way in humans compared to other hominins.…”

mentioning

confidence: 77%

A catalog of single nucleotide changes distinguishing modern humans from archaic hominins

Kuhlwilm

Boeckx

2018

Preprint

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10Throughout the past decade, studying ancient genomes provided unique insights into human 11 prehistory, and differences between modern humans and other branches like Neanderthals can 12 enrich our understanding of the molecular basis of the human condition. Modern human variation 13 and the interactions between different hominin lineages are now well studied, making it reasonable 14 to explore changes that are observed at high frequency in present-day humans, but do not reach 15 fixation. Here, we put forward interpretation of putative single nucleotide changes in recent modern 16 human history, focusing on 571 genes with non-synonymous changes at high frequency. We 17 suggest that molecular mechanisms in cell division and networks affecting cellular features of 18 neurons were prominently modified by these changes. Complex phenotypes in brain growth 19 trajectory and cognitive traits are likely influenced by these networks and other changes presented 20here. We propose that at least some of these changes contributed to uniquely human traits.

show abstract

Mechanisms behind Topoisomerase II SUMOylation in chromosome segregation

Cited by 12 publications

References 7 publications

A catalog of single nucleotide changes distinguishing modern humans from archaic hominins

A catalog of single nucleotide changes distinguishing modern humans from archaic hominins

High-content imaging-based pooled CRISPR screens in mammalian cells

A catalog of single nucleotide changes distinguishing modern humans from archaic hominins

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