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dictyNews

Electronic Edition

Volume 45, number 12

April 19, 2019



Please submit abstracts of your papers as soon as they have been

accepted for publication by sending them to [log in to unmask]

or by using the form at

http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit.



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=========

Abstracts

=========



The fate of cells undergoing spontaneous DNA damage during 

development



Agnes Miermont, Vlatka Antolovic, Tchern Lenn, John M. E. Nichols, 

Lindsey J. Millward, Jonathan R. Chubb





Development, in press



Embryonic development involves extensive and often rapid cell 

proliferation. An unavoidable side effect of cell proliferation is DNA 

damage. The consequences of spontaneous DNA damage during 

development are not clear. Here we define an approach to determine 

the effects of DNA damage on cell fate choice. Using single cell 

transcriptomics, we identified a sub-population of Dictyostelium cells 

experiencing spontaneous DNA damage. Damaged cells displayed 

high expression of rad51, with the gene induced by multiple types of 

genotoxic stress. Using live imaging, we tracked high Rad51 cells 

from differentiation onset until cell fate assignment. High Rad51 cells 

were shed from multicellular structures, excluding damaged cells 

from the spore population. Cell shedding resulted from impaired cell 

motility and defective cell-cell adhesion, with damaged cells 

additionally defective in activation of spore gene expression. These 

data indicate DNA damage is not insulated from other aspects of cell 

physiology during development and multiple features of damaged 

cells prevent propagation of genetic error. Our approach is generally 

applicable for monitoring rare sub-populations during development, 

and permits analysis of developmental perturbations occurring within 

a physiological dynamic range.





submitted by:  Jonathan Chubb [[log in to unmask]]

——————————————————————————————————————





Derivatives of Dictyostelium differentiation-inducing factors inhibit 

serum-dependent cell migration of murine osteosarcoma LM8 cells



Yuzuru Kubohara 1,2,*, Haruhisa Kikuchi 3, Yoshiteru Oshima 3,4



1 Laboratory of Health and Life Science, Juntendo University Graduate 

School of Health and Sports Science, Inzai, Chiba 270-1695, Japan

2 Department of Molecular and Cellular Biology, Institute for Molecular 

and Cellular Regulation (IMCR), Gunma University, Maebashi 371-8512, 

Japan

3 Laboratory of Natural Products Chemistry, Tohoku University Graduate 

School of Pharmaceutical Sciences, Aoba-ku, Sendai 980-8578, Japan

4 United Centers for Advanced Research and Translational Medicine 

(ART), Tohoku University Graduate School of Medicine, Aoba-ku, 

Sendai 980-8575, Japan

*Corresponding author 





Juntendo Medical Journal (Open access J.)

(https://www.jstage.jst.go.jp/article/jmj/65/1/65_JMJ18-OA10/_pdf/-char/en)



Objective: Differentiation-inducing factor-1 (DIF-1) and -3 are novel lead 

anti-tumor agents that were originally isolated from the cellular slime mold 

Dictyostelium discoideum. We previously showed that the DIF derivatives 

Br-DIF-1, DIF-3(+2), and Bu-DIF-3 strongly suppress lysophosphatidic acid 

(LPA)-induced cell migration in mouse osteosarcoma LM8 cells in vitro. 

Here, we investigated the effects of these three DIF derivatives on the cell 

migration (wound healing) of LM8 cells and mouse 3T3-L1 fibroblast cells 

(a model of non-transformed cells). 

Methods: A wound healing assay was performed to estimate the anti-cell 

migration activities of the compounds; cell growth was assessed by using 

a cell number indicator. 

Results: After monolayers of LM8 cells or 3T3-L1 cells were wounded by 

scratching and incubated with 10% serum-containing media for 20 h or 8 h, 

respectively, cell-free areas (wounds) in the monolayer were occupied 

(healed) by neighboring cells to some extent even in the presence of Ara-C 

(an inhibitor of cell proliferation). This phenomenon is attributed to the 

migration of the neighboring cells into the wounds. Wound healing (cell 

migration) of LM8 cells was strongly suppressed in the presence of 10 uM 

Br-DIF-1, DIF-3(+2), or Bu-DIF-3. These DIF derivatives more effectively 

suppressed the cell migration of LM8 cells than of 3T3-L1 cells. 

Conclusion: The results support our expectation that these DIF derivatives 

are promising lead anti-metastatic agents that may not affect normal cell 

migration.





submitted by:  Yuzuru Kubohara [[log in to unmask]]

==============================================================

[End dictyNews, volume 45, number 12]

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