Mechanism of cell death resulting from DNA interstrand cross-linking in mammalian cells

作者：Osawa T; Davies D; Hartley J A^*

来源：Cell Death & Disease, 2011, 2(8): e187.

DOI：10.1038/cddis.2011.70

• DNA interstrand cross-link
• DNA cross-link repair
• apoptosis
• cell-cycle arrest
• homologous recombination
• chromosomal abnormality

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

• 出版日期2011-8