Figure 5

Models for initiation of RAD51- and RAD59- dependent and –independent HR by defective lagging strand synthesis. 1.) Accumulation of daughter strand nicks in the absence of Rad27 nuclease causes replication fork stalling during the next S phase when the lagging strand becomes the template for leading strand synthesis and the replication fork encounters the discontinuity. 2.) The stalled fork is converted into an intact chromatid and a single-ended DSB. The single-ended DSB becomes a substrate for RAD51- and RAD59-independent HR mechanisms, such as interstitial and terminal LOH (Additional file 1: Figure S3). 3.) The replication fork from an upstream replicon converges with the previously stalled fork. 4.) Converged forks are converted into an intact chromatid and a double-ended DSB. The double-ended DSB becomes a substrate for RAD51- and RAD59-dependent HR mechanisms, such as ectopic gene conversion and heteroallelic recombination (Figures 3A and 4A).