DNA-Damage Response during Mitosis Induces Whole-Chromosome Missegregation
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Cites background from "DNA-Damage Response during Mitosis ..."
...To close the loop, it has been recently shown that activating the DNA damage response during mitosis by DNA-damaging drugs or ionizing radiation resulted in increased chromosome missegregation through stabilization of kinetochore-microtubule interactions by Aurora A and PLK1 kinases [121]....
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"DNA-Damage Response during Mitosis ..." refers background in this paper
...To this end, we exposed cells to chloroquine, an independent activator of ATM kinase (18)....
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1,197 citations
"DNA-Damage Response during Mitosis ..." refers background in this paper
...KU55933, an inhibitor of activated ATM kinase (16), completely abolished the effects of doxorubicin on k-MT stability in metaphase cells (Fig....
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"DNA-Damage Response during Mitosis ..." refers background in this paper
...However, cancer cells often encounter DNA damage during mitosis secondary to checkpoint slippage with persistence of premitotic damage (3)...
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...However, it was recently shown that premitotic replication stress, which leads to DNA damage that can persist into mitosis, is also a feature of colorectal cell lines with w-CIN (3)....
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...Anaphase spindles can also exhibit bridged chromatin (3, 11) such that DNA, from the same chromosome or from nondisjoined sister chromatids, is stretched toward opposite spindle poles (Fig....
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664 citations
"DNA-Damage Response during Mitosis ..." refers background in this paper
...Here, we show that activation of the DNA-damage response (DDR) during mitosis selectively stabilizes kinetochore–microtubule (k-MT) attachments to chromosomes through Aurora-A and PLK1 kinases, thereby increasing the frequency of lagging chromosomes during anaphase....
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...Yet, there was an increase in the levels of phospho–Centromere protein A (pCENP-A), which is also phosphorylated by Aurora-A kinase (Supplementary Fig....
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...Upon DNA damage, CHK1 and CHK2 inhibit mitotic entry by deregulating Pololike kinase 1 (PLK1) whose subsequent activation by AuroraA is required for checkpoint recovery (1, 2)....
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...Tubulin-specific DM1α (Sigma-Aldrich), anti-centromere (CREST; Dartmouth College, Hanover, NH), HEC1/NDC80-specific (Novus Biologicals), anti–γ-H2AX (Novus Biologicals), GFP-specific (William Wickner, Dartmouth College, Hanover, NH), anti-pCHK2 S19 and S33/35 (Cell Signaling Technology), anti-CHK2 (Cell Signaling Technology), anti–pPLK1-Thr210 (Cell Signaling Technology), anti–pAurora-A antibodies were used at dilutions of 1:1,000 (1:10,000 for anti-GFP antibody)....
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...Collectively, these results suggest that the DDR signals through Aurora-A and PLK1 to increase k-MT stability in response to mitotic DNA damage....
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