Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital, Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
J Cell Biol. 2012 Dec 10;199(6):871-81. doi: 10.1083/jcb.201210040.
Cellular defects that impair the fidelity of mitosis promote chromosome missegregation and aneuploidy. Increasing evidence reveals that errors in mitosis can also promote the direct and indirect acquisition of DNA damage and chromosome breaks. Consequently, deregulated cell division can devastate the integrity of the normal genome and unleash a variety of oncogenic stimuli that may promote transformation. Recent work has shed light on the mechanisms that link abnormal mitosis with the development of DNA damage, how cells respond to such affronts, and the potential impact on tumorigenesis.
细胞缺陷会损害有丝分裂的保真度,从而促进染色体错分和非整倍体。越来越多的证据表明,有丝分裂中的错误也可以促进 DNA 损伤和染色体断裂的直接和间接获得。因此,细胞分裂失控会破坏正常基因组的完整性,并释放出各种可能促进转化的致癌刺激物。最近的研究揭示了将异常有丝分裂与 DNA 损伤的发展联系起来的机制,细胞如何应对这些挑战,以及对肿瘤发生的潜在影响。