Recognition of DNA damage by PCNA-containing replication complex

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R-HSA-110314
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Homo sapiens
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Damaged double strand DNA (dsDNA) cannot be successfully used as a template by replicative DNA polymerase delta (POLD) and epsilon (POLE) complexes (Hoege et al. 2002). When the replication complex composed of PCNA, RPA, RFC and POLD or POLE stalls at a DNA damage site, PCNA becomes monoubiquitinated by RAD18 bound to UBE2B (RAD6). POLD or POLE dissociate from monoubiquitinated PCNA, while Y family DNA polymerases - REV1, POLH (DNA polymerase eta), POLK (DNA polymerase kappa) and POLI (DNA polymerase iota) - bind monoubiquitinated PCNA through their ubiquitin binding and PCNA binding motifs, resulting in a polymerase switch and initiation of translesion synthesis (TLS) (Hoege et al. 2002, Friedberg et al. 2005).

Literature References
PubMed ID Title Journal Year
12226657 RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO

Hoege, C, Pfander, B, Moldovan, GL, Pyrowolakis, G, Jentsch, S

Nature 2002
15916957 Trading places: how do DNA polymerases switch during translesion DNA synthesis?

Friedberg, EC, Lehmann, AR, Fuchs, RP

Mol. Cell 2005
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