Skip to main content
. Author manuscript; available in PMC: 2011 May 4.
Published in final edited form as: Cell Res. 2008 Jan;18(1):99–113. doi: 10.1038/cr.2008.1

Figure 3.

Figure 3

Homologous recombination and repair of DNA interstrand crosslinks. Possible pathways to resolve replication forks stalled at interstrand crosslinks. The stalled replication fork is recognized and cleaved by a specific endonuclease (hMus81-Eme1 [144]) in the leading-strand template to generate a one-sided DSB (steps 1–3). Introduction of a second incision on the other side of the ICL (step 4a) allows the lesion to flip out and to be bypassed by TLS (green line). The DSB is processed to form a 3′-OH ending single-stranded tail (step 5a) and to initiate DNA strand invasion (step 6a). The replication fork is restored (steps 7a) and the lesion is bypassed by TLS (green line). The lesion is eventually repaired, either after HR as drawn in step 8 or before (e.g. at step 5a). The DSB can also initiate DNA strand invasion using the homolog as a template (step 4b). DNA is synthesized across the lesion region (step 5b), disengaged (step 6b) and reinvasion of the sister chromatid behind the lesion site can lead to restoration of the replication fork and tolerance of the lesion (7b; the step from D-loop to recovered fork are not drawn and equivalent to Figure 2A, steps 3a–4a–5a). The hypothetical steps for ICL repair by nucleotide excision repair are not drawn here. For additional schemes for ICL repair/tolerance at stalled replication forks or in non-replicating DNA see refs. [138, 139, 145].