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Double-strand break repair-adox: Restoration of suppressed double-strand break repair during mitosis induces genomic instability.

Terasawa M, Shinohara A, Shinohara M - Cancer Sci. (2014)

Bottom Line: The failure of this process often results in apoptosis or genomic instability, such as aneuploidy, deletion, or translocation.The biological significance of this suppression is not known.We discuss how DSBs during mitosis are toxic and the multiple safeguard systems that suppress genomic instability.

View Article: PubMed Central - PubMed

Affiliation: Institute for Protein Research, Osaka University, Osaka, Japan.

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Related in: MedlinePlus

Effect of etoposide-induced double-strand breaks (DSBs) during mitosis on genomic instability of mitotic chromosomes. Representative images of chromosome spreads from etoposide-treated (+Etoposide) and non-treated (−Etoposide) in HCT116 human colon cancer cells arrested in mitosis. Arrows indicate dicentric chromosomes. Arrowheads show fragmented chromosomes. Scale bar = 10 μm.
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fig02: Effect of etoposide-induced double-strand breaks (DSBs) during mitosis on genomic instability of mitotic chromosomes. Representative images of chromosome spreads from etoposide-treated (+Etoposide) and non-treated (−Etoposide) in HCT116 human colon cancer cells arrested in mitosis. Arrows indicate dicentric chromosomes. Arrowheads show fragmented chromosomes. Scale bar = 10 μm.

Mentions: Human cells show a different DDR during mitosis than in other cell cycle phases. During most of the cell cycle, cells induce checkpoints in response to DNA damage. Until late prophase, the entry into mitosis can be suppressed by the damage. After cells reach the point of no return, however, DSBs on mitotic chromosomes do not trigger cell-cycle delay or arrest; and the cells rather proceed through mitosis even if they contain unrepaired DSBs or fragmented chromosomes.(32) Indeed, the sensitivity to ionizing radiation is higher in mitotic cells than in interphase cells.(33,34) Moreover, DSB introduction into mitotic cells by etoposide treatment induces massive chromosome aberrations in the next cell cycle in a cancer cell line (Fig. 2). Thus, DSBs during mitosis are very toxic to cells because of the induction of severe genomic instability. However, the biological significance of suppression of the DDR remains unclear.


Double-strand break repair-adox: Restoration of suppressed double-strand break repair during mitosis induces genomic instability.

Terasawa M, Shinohara A, Shinohara M - Cancer Sci. (2014)

Effect of etoposide-induced double-strand breaks (DSBs) during mitosis on genomic instability of mitotic chromosomes. Representative images of chromosome spreads from etoposide-treated (+Etoposide) and non-treated (−Etoposide) in HCT116 human colon cancer cells arrested in mitosis. Arrows indicate dicentric chromosomes. Arrowheads show fragmented chromosomes. Scale bar = 10 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317954&req=5

fig02: Effect of etoposide-induced double-strand breaks (DSBs) during mitosis on genomic instability of mitotic chromosomes. Representative images of chromosome spreads from etoposide-treated (+Etoposide) and non-treated (−Etoposide) in HCT116 human colon cancer cells arrested in mitosis. Arrows indicate dicentric chromosomes. Arrowheads show fragmented chromosomes. Scale bar = 10 μm.
Mentions: Human cells show a different DDR during mitosis than in other cell cycle phases. During most of the cell cycle, cells induce checkpoints in response to DNA damage. Until late prophase, the entry into mitosis can be suppressed by the damage. After cells reach the point of no return, however, DSBs on mitotic chromosomes do not trigger cell-cycle delay or arrest; and the cells rather proceed through mitosis even if they contain unrepaired DSBs or fragmented chromosomes.(32) Indeed, the sensitivity to ionizing radiation is higher in mitotic cells than in interphase cells.(33,34) Moreover, DSB introduction into mitotic cells by etoposide treatment induces massive chromosome aberrations in the next cell cycle in a cancer cell line (Fig. 2). Thus, DSBs during mitosis are very toxic to cells because of the induction of severe genomic instability. However, the biological significance of suppression of the DDR remains unclear.

Bottom Line: The failure of this process often results in apoptosis or genomic instability, such as aneuploidy, deletion, or translocation.The biological significance of this suppression is not known.We discuss how DSBs during mitosis are toxic and the multiple safeguard systems that suppress genomic instability.

View Article: PubMed Central - PubMed

Affiliation: Institute for Protein Research, Osaka University, Osaka, Japan.

Show MeSH
Related in: MedlinePlus