Chromosomal breaks during mitotic catastrophe trigger γH2AX–ATM–p53-mediated apoptosis

Abstract

) relating to the article 'Chromosomal breaks during mitotic catastrophe trigger γH2AX-ATM-p53-mediated apoptosis' by Gabriela Imreh, Helin Vakifahmetoglu Norberg, Stefan Imreh and Boris Zhivotovsky. J. Cell Sci. 2011Sci. 124, 2951Sci. -2963Sci. (doi: 10.1242).Concerns were raised regarding some of the data in Fig. 1A of the above-named paper. An investigation carried out by Karolinska Institutet concluded that no wrongdoing had occurred, and that no further action was required. An in-house review of the original data by Journal of Cell Science reached a similar conclusion.Journal of Cell Science is publishing this Note to alert readers that the concerns raised about this paper have been resolved. This course of action follows the advice set out by COPE (Committee on Publication Ethics), of which Journal of Cell Science is a member. Concerns have been raised regarding some of the data in Fig. 1A of the above-named paper. Journal of Cell Science is publishing this note to make readers aware of this issue, and we will provide further information once the issue has been resolved. 3419This course of action follows the advice set out by COPE (Committee on Publication Ethics), of which Journal of Cell Science is a member. There was an error published in J. Cell Sci. 124, 2951-2963. 1979In Fig. 4C, the blot representing pATM was inadvertently duplicated as representing G3PDH. The G3PDH western blot has been replaced with the correct image in the figure shown below. There are no changes to the figure legend, which is accurate. This error does not affect the conclusions of the study.The authors apologise to the readers for any confusion that this error might have caused. Fig. 4. Increased γH2AX level during MC leads to cell death. Untreated or doxorubicin (600 nM)-treated 14-3-3σ-knockout HCT116 cells were cultured and harvested at indicated time points and analysed by western blot (50 μg), comet assay and immunostaining using antibodies directed against γH2AX (green). Blots were reprobed for G3PDH to confirm an equal loading of the samples. The co-staining of nuclei was performed using Hoechst 33342 (white). (A,B) Representative confocal images showing nuclear morphology and γH2AX staining in 14-3-3σ-knockout HCT116 (A) or wild-type HCT116 (B) cells after treatment for indicated time. (C) 14-3-3σ-knockout HCT116 cells were treated for 9 hours with doxorubicin after which the culture medium was replaced and cells were grown for an additional 24, 48 and 72 hours. Immunoblots of p53, phosphorylated ATM and γH2AX are shown. (D) Doxorubicin-induced DNA damage measured by alkaline comet assay. Cells were analysed by fluorescence microscopy and scored according to tail moment. Error bars represent the mean of three independent experiments±s.e.m. Scale bar: 20 μm. Science (2016Science ( ) 129, 1950Science ( doi:10.1242 © 2016. Published by The Company of Biologists Ltd | Journal of Cell Journal of Cell ScienceChromosomal breaks during mitotic catastrophe trigger cH2AX-ATM-p53-mediated apoptosis Summary Although the cause...

Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha–Targeting Antibody-Drug Conjugate, Potentiates the Activity of Standard of Care Therapeutics in Ovarian Cancer Models

“…Consistent with these results, co-treatment with both agents resulted in almost half of all viable cells accumulating in G2/M. We also examined expression changes in the phosphorylated form of histone H2AX (γH2AX), a sensitive indicator of DNA damage that occurs in response to alkylating agents or as a result of mitotic catastrophe [42], [43]. Single-agent IMGN853 treatment induced γH2AX expression in IGROV-1 cells and to levels higher than those seen following carboplatin exposure alone.…”

Arsenic trioxide amplifies cisplatin toxicity in human tubular cells transformed by HPV-16 E6/E7 for further therapeutic directions in renal cell carcinoma

“…As p53 is a major mediator of ATM kinase-regulated DDR, and after DNA damage, may activate cell cycle restriction or apoptosis (21), we determined whether cell growth alterations involved this mechanism. To dissect limbs of p53 signaling, we used well-characterized small molecule drugs (22–24).…”

Regulatory mechanisms and clinical perspectives of miRNA in tumor radiosensitivity

“…In addition, inhibiting ATM, ATR and downstream proteins, such as Cdc25A, Chk1, Chk2, Cdk2, p53, p21, PLK1 or WEE1, can improve tumor radiosensitivity and hinder the DNA damage repair process [38]. Apoptosis is controlled by ATM and ATR and altering the function of apoptosis-associated proteins, such as p53, FAS, PUMA and Bax, could promote apoptosis and enhance radiotherapeutic effects [39–40]. …”