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

Toxicology

Journal of Clinical Toxicology

Author(s): Huang H, Fletcher L, Beeharry N, Daniel R, Kao G,

Abstract Share this page

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. This article was published in Cancer Res and referenced in Journal of Clinical Toxicology

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords