Journal
CELL DEATH & DISEASE
Volume 2, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2011.70
Keywords
DNA interstrand cross-link; DNA cross-link repair; apoptosis; cell-cycle arrest; homologous recombination; chromosomal abnormality
Categories
Funding
- Cancer Research UK [C2259/A9994]
- Cancer Research UK [9994] Funding Source: researchfish
- Grants-in-Aid for Scientific Research [23701047] Funding Source: KAKEN
Ask authors/readers for more resources
DNA interstrand cross-links (ICLs) are critical cytotoxic lesions produced by cancer chemotherapeutic agents such as the nitrogen mustards and platinum drugs; however, the exact mechanism of ICL-induced cell death is unclear. Here, we show a novel mechanism of p53-independent apoptotic cell death involving prolonged cell-cycle (G(2)) arrest, ICL repair involving HR, transient mitosis, incomplete cytokinesis, and gross chromosomal abnormalities resulting from ICLs in mammalian cells. This characteristic 'giant' cell death, observed by using time-lapse video microscopy, was reduced in ICL repair ERCC1- and XRCC3-deficient cells. Collectively, the results illustrate the coordination of ICL-induced cellular responses, including cell-cycle arrest, DNA damage repair, and cell death. Cell Death and Disease (2011) 2, e187; doi: 10.1038/cddis.2011.70; published online 4 August 2011
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available