Sion polymerases and such as rescue by convergent forks, recruitment of translesion polymerases and template template-switching. In response to inter-strand cross-links (ICLs) which block replisome progression, switching. In response to LY156758 (free base) Data Sheet interstrand crosslinks (ICLs) which block replisome progression, the the Fanconi Anemia (FA) repair pathway is engaged to remove covalent bonds in between DNA strands Fanconi Anemia (FA) repair pathway is engaged to take away covalent bonds among DNA strands and full DNA C3G/Crk Inhibitors Reagents replication [103]. Stalled forks could also be processed by structure-specific and comprehensive DNA replication [103]. Stalled forks may well also be processed by structurespecific endonucleases into single-ended double-stranded DNA breaks (DSBs) which can then be repaired byby endonucleases into singleended doublestranded DNA breaks (DSBs) which can then be repaired recombination-dependent pathways such as break-induced replication [14,15]. recombinationdependent pathways for example breakinduced replication [14,15].Figure 1. 1. Replicationfork Reversal and Restart Pathways. Stalled forks are rapidly reversed into four Figure Replication fork Reversal and Restart Pathways. Stalled forks are rapidly reversed into four-branched structures by the combined activities of numerous DNA helicases. Stalled forks could be branched structures by the combined activities of a number of DNA helicases. Stalled forks can be rescued a a converging fork arising from nearbyfired origin or by activation of local dormant rescued bybyconverging fork arising from aanearby-fired origin or by activation of aa nearby dormant origin the replication anxiety response. Within the occasion replication fork stalling because of broken bases, origin by by the replication strain response. Inthe event of replication fork stalling because of damaged bases, errorprone translesion polymerases can replicate previous the problematic lesions. Alternatively, stalled error-prone translesion polymerases can replicate previous the problematiclesions. Alternatively, stalled polymerases can use undamaged template to help genome replication, most generally this template polymerases can use anan undamaged template to help genome replication,most typically this template is theis the newlysynthesized strand on thechromatid. Stalled Stalled forks can nucleolytically processed newly-synthesized strand on the sister sister chromatid. forks may also be also be nucleolytically processed (isosceles triangle) to yield singleended DSBs that are repaired by recombinationbased (isosceles triangle) to yield single-ended DSBs which can be repaired by recombination-based pathways. pathways. The most effective characterized interstrand repair mechanism needs the convergence of two The ideal characterized inter-strand cross-link crosslink repair mechanism calls for the convergence of two forks in the lesion but replication-independent repair can also happen. Single occur. Single replication replication forks at the lesion but replicationindependent repair can alsoreplication forks replication forks often which permits post-replicative repair of the lesion. Nucleases lesion. often traverse cross-links traverse crosslinks which permits postreplicative repair of the(isosceles Nucleases (isosceles triangles) incise triangles) incise a single DNA strand ina5single 3 on the cross-link therebythe crosslink thereby building and DNA strand in five and 3 of building a double-strand break a doublestrand break (DSB) concomitantly with crosslink unhooking. Translesio.