Pipettes And Politics

The study of DNA damage has broad relevance to human pathophysiology with its involvement in birth defects, cancer, premature aging syndromes, and certain neurologic disorders. Single strand breaks (SSBs) are among the most common form of endogenous DNA damage. Here we will describe mechanisms by which SSBs threaten genome integrity in mitotic and post-mitotic cells. If they are not resolved in a timely manner, SSBs can derail passing replication forks converting them to toxic double strand breaks (DSBs). These so called “collapsed forks” arise spontaneously in every S phase and are believed to be the primary physiological trigger of homologous recombination. We will describe a recent study using the CRISPR/Cas9 nicking enzymes to examine the interaction of the human replication machinery with SSBs. We combine direct analyses of DNA end structures at sites of DNA nick-induced fork collapse with detailed mapping of repair factor binding to establish a comprehensive high-resolution view of how replication-coupl