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The heterogenic final cell cycle of chicken retinal Lim1 horizontal cells is not regulated by the DNA damage response pathway
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
2014 (English)In: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 13, no 3, 408-417 p.Article in journal (Refereed) Published
Abstract [en]

Cells with aberrations in chromosomal ploidy are normally removed by apoptosis. However, aneuploid neurons have been shown to remain functional and active both in the cortex and in the retina. Lim1 horizontal progenitor cells in the chicken retina have a heterogenic final cell cycle, producing some cells that enter S-phase without proceeding into M-phase. The cells become heteroploid but do not undergo developmental cell death. This prompted us to investigate if the final cell cycle of these cells is under the regulation of an active DNA damage response. Our results show that the DNA damage response pathway, including gamma-H2AX and Rad51 foci, is not triggered during any phase of the different final cell cycles of horizontal progenitor cells. However, chemically inducing DNA adducts or double-strand breaks in Lim1 horizontal progenitor cells activated the DNA damage response pathway, showing that the cells are capable of a functional response to DNA damage. Moreover, manipulation of the DNA damage response pathway during the final cell cycle using inhibitors of ATM/ATR, Chk1/2, and p38MAPK, neither induced apoptosis nor mitosis in the Lim1 horizontal progenitor cells. We conclude that the DNA damage response pathway is functional in the Lim1 horizontal progenitor cells, but that it is not directly involved in the regulation of the final cell cycle that gives rise to the heteroploid horizontal cell population.

Place, publisher, year, edition, pages
2014. Vol. 13, no 3, 408-417 p.
Keyword [en]
Rad51, ATM/ATR, retina, apoptosis, cell cycle regulation, H2AX, DNA damage response, programmed cell death, cisplatin
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-223571DOI: 10.4161/cc.27200ISI: 000332833400016OAI: oai:DiVA.org:uu-223571DiVA: diva2:713992
Available from: 2014-04-24 Created: 2014-04-22 Last updated: 2017-12-05Bibliographically approved

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Fard, Shahrzad ShiraziHallböök, Finn

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