A role for PCNA ubiquitination in immunoglobulin hypermutation

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Abstract

Proliferating cell nuclear antigen (PCNA) is a DNA polymerase cofactor and regulator of replication-linked functions. Upon DNA damage, yeast and vertebrate PCNA is modified at the conserved lysine K164 by ubiquitin, which mediates error-prone replication across lesions via translesion polymerases. We investigated the role of PCNA ubiquitination in variants of the DT40 B cell line that are mutant in K164 of PCNA or in Rad18, which is involved in PCNA ubiquitination. Remarkably, the PCNAK164R mutation not only renders cells sensitive to DNA-damaging agents, but also strongly reduces activation induced deaminase-dependent single-nucleotide substitutions in the immunoglobulin light-chain locus. This is the first evidence, to our knowledge, that vertebrates exploit the PCNA-ubiquitin pathway for immunoglobulin hypermutation, most likely through the recruitment of error-prone DNA polymerases. © 2006 Arakawa et al.

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APA

Arakawa, H., Moldovan, G. L., Saribasak, H., Saribasak, N. N., Jentsch, S., & Buerstedde, J. M. (2006). A role for PCNA ubiquitination in immunoglobulin hypermutation. PLoS Biology, 4(11), 1947–1956. https://doi.org/10.1371/journal.pbio.0040366

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