Abnormal cytokinesis after X-irradiation in tumor cells that override the G2 DNA damage checkpoint.

Huang, H; Fletcher, L; Beeharry, N; Daniel, R; Kao, G; Yen, T; Muschel, R

Journal article

Abnormal cytokinesis after X-irradiation in tumor cells that override the G2 DNA damage checkpoint.

Abstract:: X-irradiation-induced DNA damage perturbs the G(1), S, and G(2) phases of the cell cycle. The behavior of cells after they have experienced a DNA damage checkpoint delay is poorly characterized. We therefore examined the fates of irradiated tumor cells that have overcome a prolonged G(2) checkpoint delay. Most irradiated cells progressed through mitosis without significant delay, but failed to complete cytokinesis as they remained tethered to each other at the midbody. We observed that the movement of centrioles at the time of cytokinesis was impaired in the irradiated, bridged cells. We attribute the perturbation of centriole dynamics to the presence of chromatin bridges that spanned the daughter cells. The bridged cells exhibited different fates that included death, fusion that formed multinucleated cells, or another round of mitosis with no noticeable cell cycle delays. The presence of gammaH2AX foci in the bridge as well as in the separated nuclei indicated that cells were proliferating despite the presence of DNA damage. It seems that DNA damage checkpoints were not reactivated in cells that overrode a prolonged G(2) delay. Cells deficient in ATM, H2AX, XRCC3, or ligase 4 exhibited a higher frequency of radiation-induced bridges than controls, suggesting that the DNA bridges resulted from inadequate DNA repair. These data show a previously unappreciated cytologic hallmark of DNA damage in dividing cells. Chromatin bridges that interfere with cytokinesis are likely to contribute to the replication failure and clonogenic death of cells exposed to irradiation.

Publication status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Huang, H., Fletcher, L., Beeharry, N., Daniel, R., Kao, G., Yen, T., & Muschel, R. (2008). Abnormal cytokinesis after X-irradiation in tumor cells that override the G2 DNA damage checkpoint. Cancer Research, 68(10), 3724–3732.

MLA Style

Huang, H, et al. “Abnormal Cytokinesis after X-Irradiation in Tumor Cells That Override the G2 DNA Damage Checkpoint.” Cancer Research, vol. 68, no. 10, 2008, pp. 3724–32.

Chicago Style

Huang, H, L Fletcher, N Beeharry, et al. 2008. “Abnormal Cytokinesis after X-Irradiation in Tumor Cells That Override the G2 DNA Damage Checkpoint.” Cancer Research 68 (10): 3724–32.
Print