RAD18 and ubiquitinated PCNA-mediated recruitment of translesion polymerases

Stable Identifier
R-GGA-353299
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Pathway
Species
Gallus gallus
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ReviewStatus
5/5
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Proliferating cell nuclear antigen (PCNA) is a DNA polymerase cofactor and regulator of replication linked functions. Upon DNA damage, vertebrate PCNA is modified at the conserved K164 residue by ubiquitin. Ubiquitinated PCNA mediates error prone replication across lesions via recruitment of translesion polymerases. The PCNA (K164R) mutation not only renders cells sensitive to DNA damaging agents but also strongly reduces activation-induced deaminase(AID) dependent single nucleotide substitutions in the immunoglobulin light chain locus. Somatic hypermutation of Ig genes is initiated by transcription coupled cytidine deamination in the Ig loci. Rad6/Rad18 mediated ubiquitination of PCNA, thus, is a major regulatory point controlling the fidelity of DNA lesions for immunoglobulin hypermutation during the mutagenesis phase of secondary Ig diversification. Thus, an unanticipated role for Rad18, the major participant of error-free HR-mediated DNA repair; in regulating error-prone damage bypass has been identified.
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