Reactome | Recognition of DNA damage by PCNA-containing replication complex

Recognition of DNA damage by PCNA-containing replication complex

Stable Identifier

R-HSA-110314

Type

Pathway

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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Recognition of DNA damage by PCNA-containing replication complex

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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
15916957	Trading places: how do DNA polymerases switch during translesion DNA synthesis? Friedberg, EC, Lehmann, AR, Fuchs, RP	Mol. Cell	2005
12226657	RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO Moldovan, GL, Hoege, C, Pfander, B, Pyrowolakis, G, Jentsch, S	Nature	2002