Monoubiquitunated PCNA mediates recruitment of the translesion polymerase to the DNA damaged site.

Stable Identifier
R-GGA-353243
Type
Reaction [binding]
Species
Gallus gallus
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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.

Literature References
PubMed ID Title Journal Year
16357182 Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells

Nojima, K, Hochegger, H, Saberi, A, Fukushima, T, Kikuchi, K, Yoshimura, M, Orelli, BJ, Bishop, DK, Hirano, S, Ohzeki, M, Ishiai, M, Yamamoto, K, Takata, M, Arakawa, H, Buerstedde, JM, Yamazoe, M, Kawamoto, T, Araki, K, Takahashi, JA, Hashimoto, N, Takeda, S, Sonoda, E

Cancer Res 2005
16873544 Involvement of Rad18 in somatic hypermutation

Bachl, J, Ertongur, I, Jungnickel, B

Proc Natl Acad Sci U S A 2006
16931176 A novel Rad18 function involved in protection of the vertebrate genome after exposure to camptothecin

Yoshimura, A, Nishino, K, Takezawa, J, Tada, S, Kobayashi, T, Sonoda, E, Kawamoto, T, Takeda, S, Ishii, Y, Yamada, K, Enomoto, T, Seki, M

DNA Repair (Amst) 2006
12374756 RAD18 and RAD54 cooperatively contribute to maintenance of genomic stability in vertebrate cells

Yamashita, YM, Okada, T, Matsusaka, T, Sonoda, E, Zhao, GY, Araki, K, Tateishi, S, Yamaizumi, M, Takeda, S

EMBO J 2002
17105346 A role for PCNA ubiquitination in immunoglobulin hypermutation

Arakawa, H, Moldovan, GL, Saribasak, H, Saribasak, NN, Jentsch, S, Buerstedde, JM

PLoS Biol 2006
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