The Role of Proliferating Cell Nuclear Antigen (PCNA) in Predicting Biologic Behavior of Lymphoid Infiltrates of the Orbit and Ocular Adnexae

Proliferating cell nuclear antigen (PCNA) encircles DNA as a ring-shaped homotrimer and, by tethering DNA polymerases to their template, PCNA serves as a critical replication factor. In contrast to high-fidelity DNA polymerases, the activation of low-fidelity translesion synthesis (TLS) DNA polymerases seems to require damage-inducible monoubiquitylation (Ub) of PCNA at lysine residue 164 (PCNA-Ub). TLS polymerases can tolerate DNA damage, i.e. they can replicate across DNA lesions. The lack of proofreading activity, however, renders TLS highly mutagenic. The advantage is that B cells use mutagenic TLS to introduce somatic mutations in immunoglobulin (Ig) genes to generate high-affinity antibodies. Given the critical role of PCNA-Ub in activating TLS and the role of TLS in establishing somatic mutations in immunoglobulin genes, we analysed the mutation spectrum of somatically mutated immunoglobulin genes in B cells from PCNA K164R knock-in mice. A 10-fold reduction in A/T mutations is associated with a compensatory increase in G/C mutations—a phenotype similar to Polη and mismatch repair-deficient B cells. Mismatch recognition, PCNA-Ub and Polη probably act within one pathway to establish the majority of mutations at template A/T. Equally relevant, the G/C mutator(s) seems largely independent of PCNA K164 modification.

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Pro-recombination Role of Srs2 Protein Requires SUMO (Small Ubiquitin-like Modifier) but Is Independent of PCNA (Proliferating Cell Nuclear Antigen) Interaction

Journal of Biological Chemistry ◽

10.1074/jbc.m115.685891 ◽

2016 ◽

Vol 291 (14) ◽

pp. 7594-7607 ◽

Cited By ~ 13

Author(s):

Peter Kolesar ◽

Veronika Altmannova ◽

Sonia Silva ◽

Michael Lisby ◽

Lumir Krejci

Keyword(s):

Proliferating Cell Nuclear Antigen ◽

Nuclear Antigen ◽

Antigen Interaction ◽

Proliferating Cell

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Purification and characterization of a 100 kDa DNA polymerase from cauliflower inflorescence

Biochemical Journal ◽

10.1042/bj3320557 ◽

1998 ◽

Vol 332 (2) ◽

pp. 557-563 ◽

Cited By ~ 21

Author(s):

Hirokazu SETO ◽

Masami HATANAKA ◽

Seisuke KIMURA ◽

Masahiko OSHIGE ◽

Yuri TSUYA ◽

...

Keyword(s):

Dna Synthesis ◽

Dna Polymerase ◽

Proliferating Cell Nuclear Antigen ◽

Nuclear Antigen ◽

Purification And Characterization ◽

Synthetic Dna ◽

Different Types ◽

Proliferating Cell

A DNA polymerase from cauliflower (Brassica oleracea var. botrytis) inflorescence has been purified to near homogeneity through five successive column chromatographies, and temporally designated cauliflower polymerase 1. Cauliflower polymerase 1 is a monopolypeptide with a molecular mass of 100 kDa. The enzyme efficiently uses synthetic DNA homopolymers and moderately activated DNA and a synthetic RNA homopolymer as template-primers. The enzyme is strongly sensitive to dideoxythymidine triphosphate and N-ethylmaleimide, but it is insensitive to aphidicolin. It was stimulated with 250 mM KCl. Its mode of DNA synthesis is high-processive with or without proliferating-cell nuclear antigen. A 3´ → 5´ exonuclease activity is associated with cauliflower polymerase 1. The enzyme is clearly different from cauliflower mitochondrial polymerase and does not resemble the four different types of wheat DNA polymerase, designated wheat DNA polymerases A, B, CI and CII. In the present paper the role of the enzyme in plant DNA synthesis is discussed.

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