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. 2021 Sep 27;12:748033. doi: 10.3389/fgene.2021.748033

FIGURE 2.

FIGURE 2

Fork restart mechanisms. (A) Fork restart mechanisms that do not create seDSBs. Illustrated are rescue by an adjacent fork, TLS, template switching, and repriming. Blocking lesions are shown by red symbols and repair or bypass synthesis is shown by red arrows. (B) Fork restart by fork regression, fork encounters with a single-strand break (SSB), or fork cleavage, which create seDSBs. Regressed forks allow synthesis past the blocking lesion using the nascent strand as template. Reverse branch migration restarts the fork, or RAD51 may load onto a resected end allowing strand invasion downstream of the blocking lesion. Blocking lesions may be bypassed or repaired, indicated by symbols in parentheses. Collapsed forks due to encounter with single-strand breaks or fork cleavage can restart by RAD51-mediated strand invasion, i.e., break-induced replication. The strand invasion restart pathways are mediated by HR; fork regression/reversal is not an HR pathway, but RAD51 is still required to protect the nascent strands in the chicken foot. HR defects and HR inhibitors may shunt seDSB intermediates to cNHEJ or aNHEJ (dashed box) causing genome instability.