Model for the relationship between ATR, homologous recombination and chromosomal stability.

<p>In the presence of replication stress from endogenous lesions, ATR is activated initiating an S-phase arrest to block aberrant merger of another replication fork at the same lesion. Some stalled replication forks will be substrates for HR (depicted here is the formation of a chicken foot structure that acts as a RAD51 substrate). If HR proceeds as normal, then the replication fork will be restored. However, we propose that this progression is dependent upon sufficient time to complete the HR reaction and possibly a more direct licensing of a later step in HR by ATR kinase activity (CHK1, BRCA1 and BLM, for example – not shown). If HR does not restore the stalled fork, then it may collapse, potentially leading to chromosomal breaks and the production of micronuclei. Thick lines are parental strand DNA, thin lines are daughter strand DNA, half arrowheads represent 3′ ends, the solid black triangle represents a DNA lesion and solid black circles represent RAD51 protein.