Two mechanisms of chromosome fragility at replication-termination sites in bacteria
Qian Mei, Devon M. Fitzgerald, Jingjing Liu, Jun Xia, John P. Pribis, Yin Zhai, Ralf B. Nehring, Jacob Paiano, Heyuan Li, André Nussenzweig, P. J. Hastings, Susan M. Rosenberg
Abstract
genome and define their DNA damage and repair intermediates at high resolution. We find that all three sites, all in the region of replication termination, display recurrent four-way DNA or Holliday junctions (HJs) and recurrent DNA breaks. Homology-directed double-strand break repair generates the recurrent HJs at all of these sites; however, distinct mechanisms of DNA breakage are implicated: replication fork collapse at natural replication barriers and, unexpectedly, frequent shearing of unsegregated sister chromosomes at cell division. We propose that mechanisms such as both of these may occur ubiquitously, including in humans, and may constitute some of the earliest events that underlie somatic cell mosaicism, cancers, and other diseases of genome instability.