The Spatiotemporal Dynamics of Chromatin Protein HP1α Is Essential for Accurate Chromosome Segregation during Cell Division

Chu, Lingluo; Huo, Yuda; Liu, Xing; Yao, Phil; Thomas, Kenneth W.; Jiang, Hao; Zhu, Tongge; Zhang, Guanglan; Chaudhry, Maryam; Adams, Gregory; Thompson, Winston E.; Dou, Zhen; Jin, Changjie; He, Ping; Yao, Xuebiao

doi:10.1074/jbc.m114.581504

Cited by 13 publications

(15 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, SUV39H1ΔSET binding did not interfere with normal mitotic progression. In contrast, other authors have observed a mitotic arrest after inhibiting SUV39H1 by its specific inhibitor chaetonin, which decreases the levels of heterochromatin (Chu et al 2014; Chu et al 2012). This stronger phenotype could be due to off-target effects of the drug or to the action of SUV39H1 on other targets required for mitotic progression.…”

Section: Discussionmentioning

confidence: 83%

PREditOR: a synthetic biology approach to removing heterochromatin from cells

2016

View full text Add to dashboard Cite

It is widely accepted that heterochromatin is necessary to maintain genomic stability. However, direct experimental evidence supporting this is slim. Previous studies using either enzyme inhibitors, gene knockout or knockdown studies all are subject to the caveat that drugs may have off-target effects and enzymes that modify chromatin proteins to support heterochromatin formation may also have numerous other cellular targets as well. Here, we describe PREditOR (protein reading and editing of residues), a synthetic biology approach that allows us to directly remove heterochromatin from cells without either drugs or global interference with gene function. We find that removal of heterochromatin perturbs mitotic progression and causes a dramatic increase in chromosome segregation defects, possibly as a result of interfering with the normal centromeric localization of the chromosomal passenger complex.Electronic supplementary materialThe online version of this article (doi:10.1007/s10577-016-9539-3) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 83%

PREditOR: a synthetic biology approach to removing heterochromatin from cells

2016

View full text Add to dashboard Cite

show abstract

“…Several mechanisms might be responsible for induction of DSBs in interphase. First, as demonstrated previously in HeLa cells, SGO1 protects cohesin on chromosomal arms during interphase via the HP1-SGO1 pathway 44 . When SGO1 is knocked down, cohesin is released from both the chromosomal arm and pericentromeric regions even in interphase, potentially resulting in DNA damage.…”

Section: Discussionmentioning

confidence: 55%

SGO1 is involved in the DNA damage response in MYCN-amplified neuroblastoma cells

Murakami-Tonami

Ikeda

Yamagishi

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Shugoshin 1 (SGO1) is required for accurate chromosome segregation during mitosis and meiosis; however, its other functions, especially at interphase, are not clearly understood. Here, we found that downregulation of SGO1 caused a synergistic phenotype in cells overexpressing MYCN. Downregulation of SGO1 impaired proliferation and induced DNA damage followed by a senescence-like phenotype only in MYCN-overexpressing neuroblastoma cells. In these cells, SGO1 knockdown induced DNA damage, even during interphase, and this effect was independent of cohesin. Furthermore, MYCN-promoted SGO1 transcription and SGO1 expression tended to be higher in MYCN- or MYC-overexpressing cancers. Together, these findings indicate that SGO1 plays a role in the DNA damage response in interphase. Therefore, we propose that SGO1 represents a potential molecular target for treatment of MYCN-amplified neuroblastoma.

show abstract

“…Chromatin is contained within compartments that are regulated spatiotemporally by cell cycle machinery and extracellular cues such as growth factors (6,48,49). Heterochromatin, situated between the pericentromere and telomeres of mitotic chromosomes, is essential for maintaining genome stability (6).…”

Section: Chromatin Plasticity and Llpsmentioning

confidence: 99%

“…Heterochromatin is involved in nuclear processes ranging from gene repression to chromosome segregation. The diversified functions of heterochromatin depend on the capacity of these structures to interact with the underlying DNA and to orchestrate various types of stimulation signals in a context-dependent manner during the cell division cycle (48,49).…”

Section: Chromatin Plasticity and Llpsmentioning

confidence: 99%

Phase separation drives decision making in cell division

Liu

Wang

et al. 2020

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Liquid-liquid phase separation (LLPS) of biomolecules drives the formation of subcellular compartments with distinct physicochemical properties. These compartments, free of lipid bilayers and therefore called membraneless organelles, include nucleoli, centrosomes, heterochromatin, and centromeres. These have emerged as a new paradigm to account for subcellular organization and cell fate decisions. Here we summarize recent studies linking LLPS to mitotic spindle, heterochromatin, and centromere assembly and their plasticity controls in the context of the cell division cycle, highlighting a functional role for phase behavior and material properties of proteins assembled onto heterochromatin, centromeres, and central spindles via LLPS. The techniques and tools for visualizing and harnessing membraneless organelle dynamics and plasticity in mitosis are also discussed, as is the potential for these discoveries to promote new research directions for investigating chromosome dynamics, plasticity, and inter-chromosome interactions in the decision-making process during mitosis.

show abstract

The Spatiotemporal Dynamics of Chromatin Protein HP1α Is Essential for Accurate Chromosome Segregation during Cell Division

Cited by 13 publications

References 49 publications

PREditOR: a synthetic biology approach to removing heterochromatin from cells

PREditOR: a synthetic biology approach to removing heterochromatin from cells

SGO1 is involved in the DNA damage response in MYCN-amplified neuroblastoma cells

Phase separation drives decision making in cell division

Contact Info

Product

Resources

About