DNA repair pathways involved in anaphase bridge formation

Cancer cells frequently exhibit gross chromosomal alterations such as translocations, deletions, or gene amplifications an important source of chromosomal instability in malignant cells. One of the better-documented examples is the formation of anaphase bridges-chromosomes pulled in opposite directions by the spindle apparatus. Anaphase bridges are associated with DNA double strand breaks (DSBs). While the majority of DSBs are repaired correctly, to restore the original chromosome structure, incorrect fusion events also occur leading to bridging. To identify the cellular repair pathways used to form these aberrant structures, we tested a requirement for either of the two major DSB repair pathways in mammalian cells: homologous recombination (HR) and nonhomologous end joining (NHEJ). Our observations show that neither pathway is essential, but NHEJ helps prevent bridges. When NHEJ is compromised, the cell appears to use HR to repair the break, resulting in increased anaphase bridge formation. Moreover, intrinsic NHEJ activity of different cell lines appears to have a positive trend with induction of bridges from DNA damage. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. (c) 2007 Wiley-Liss, Inc.