The expanding polymerase universe

Goodman, Myron F.; Tippin, Brigette L.

doi:10.1038/35040051

Cited by 152 publications

(108 citation statements)

References 98 publications

Supporting

Mentioning

108

Contrasting

Order By: Relevance

“…Escherichia coli encodes five polymerases (PolI to PolV), two of which are involved in replication, with the other three being involved in DNA repair, DNA damage tolerance and stress-induced mutagenesis 4 . By contrast, mammals have 14 such enzymes (or 15, if one includes terminal deoxynucleotidyl transferase (TdT), a template-independent polymerase).…”

Section: Dna Polymerasesmentioning

confidence: 99%

DNA polymerases in adaptive immunity

Weill

Reynaud

2008

Nat Rev Immunol

View full text Add to dashboard Cite

PrefaceTo cope with an unpredictable variety of potential pathogenic insults, the immune system must generate an enormous diversity of recognition structures, and it does so by making stepwise modifications of key genetic loci in each lymphoid cell. This proceeds through the action of lymphoid-specific proteins acting together with the general DNA-repair machinery of the cell. Strikingly, these general mechanisms are usually diverted from their normal functions, being used in rather atypical ways in order to privilege diversity over accuracy. In this Review, we focus on the contribution of a set of DNA polymerases discovered in the last decade to these unique DNA transactions.

show abstract

Section: Dna Polymerasesmentioning

confidence: 99%

DNA polymerases in adaptive immunity

Weill

Reynaud

2008

Nat Rev Immunol

View full text Add to dashboard Cite

show abstract

“…Products were resolved on a 12% polyacrylamide (8 M urea) gel. Primer extension reactions were performed on primer templates having 5Ј homopolymer extensions of poly(T) (A, lanes 1-6), poly(dC) (B, lanes 7-12), or a poly(T) extension containing two dC residues at positions 6 and 12 (C, lanes [13][14][15][16][17][18]. The arrows on the left side of the gel (B) indicate the position of the 2 Cs on the template.…”

Section: S Pyogenes Dnae Efficiently Bypasses 8-oxo-dg and 2-aminopumentioning

confidence: 99%

“…Specialized repair polymerases are required to synthesize across DNA lesions in vivo (15). Bypass of DNA lesions, or "translesion synthesis," is performed by the Y family of DNA polymerases, which are characterized by their ability to bypass lesions in synthetic DNA templates and lack an associated exonuclease (16).…”

mentioning

confidence: 99%

The Essential C Family DnaE Polymerase Is Error-prone and Efficient at Lesion Bypass

Bruck

Goodman

O'Donnell

2003

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

DnaE-type DNA polymerases belong to the C family of DNA polymerases and are responsible for chromosomal replication in prokaryotes. Like most closely related Gram-positive cells, Streptococcus pyogenes has two DnaE homologs Pol C and DnaE; both are essential to cell viability. Pol C is an established replicative polymerase, and DnaE has been proposed to serve a replicative role. In this report, we characterize S. pyogenes DnaE polymerase and find that it is highly error-prone. DnaE can bypass coding and noncoding lesions with high efficiency. Error-prone extension is accomplished by either of two pathways, template-primer misalignment or direct primer extension. The bypass of abasic sites is accomplished mainly through "dNTP-stabilized" misalignment of template, thereby generating (؊1) deletions in the newly synthesized strand. This mechanism may be similar to the dNTP-stabilized misalignment mechanism used by the Y family of DNA polymerases and is the first example of lesion bypass and error-prone synthesis catalyzed by a C family polymerase. Thus, DnaE may function in an error-prone capacity that may be essential in Gram-positive cells but not Gram-negative cells, suggesting a fundamental difference in DNA metabolism between these two classes of bacteria.

show abstract

“…Eukaryotic genomes encode multiple DNA polymerases that differ in their processivity, function, and fidelity. Members of the Y family of translesion polymerases are characterized by a flexible catalytic site that allows them to bypass bulky DNA lesions, but at the same time impairs their accuracy while copying undamaged DNA (6). The low fidelity and hence mutagenic capacity of translesion polymerases such as Pol and Rev 1 is exploited during somatic hypermutation (7,8).…”

mentioning

confidence: 99%

Involvement of Rad18 in somatic hypermutation

Brinckmann¹,

Ertongur²,

Jungnickel³

2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Somatic hypermutation of Ig genes is initiated by transcriptioncoupled cytidine deamination in Ig loci. Error-prone processing of the resultant DNA lesions is thought to cause extensive mutagenesis, but it is presently an enigma how and why error-prone rather than error-free repair pathways are recruited. During DNA replication, recruitment of error-prone translesion polymerases may be mediated by Rad6͞Rad18-mediated ubiquitination of proliferating cell nuclear antigen, a major switchboard controlling the fidelity of DNA lesion bypass in eukaryotes. By inactivation of Rad18 in the DT40 B cell line, we show that the Rad6 pathway is involved in somatic hypermutation in these cells. Our findings imply that targeted recruitment of mutagenic polymerases by the Rad6 pathway contributes to the complex process of somatic hypermutation and provide a framework for more detailed mechanistic studies of the mutagenesis phase of secondary Ig diversification.proliferating cell nuclear antigen ͉ ubiquitination ͉ Rad6 pathway G iven the many challenges that damage cellular DNA daily, the faithful maintenance of genetic information requires the interplay of multiple DNA repair pathways. In most cases, these mechanisms ensure restoration of the original DNA sequence, preventing mutations or aberrations that may lead to impairment of cellular function. In some instances, though, a certain imprecision may be tolerated or even favored by the cell to allow for survival in critical situations. DNA repair mechanisms that are inherently imprecise are the basis of the spontaneous mutability of all genomes and may be recruited and adapted for situations where high genetic variability is mandatory for survival.The adaptive immune system of vertebrates has been shaped in coevolution with pathogenic organisms of high genetic diversity and variability. The high diversity of the primary immune repertoire established during V(D)J recombination in B and T cells generates sufficient potential for recognition of any pathogen, but the affinity of binding is often not sufficient for effective neutralization. Therefore, a second wave of diversification during acute infections ensures that the binding affinity of the antibodies produced by B lymphocytes is fine-tuned to the task at hand. The underlying mechanism in humans is somatic hypermutation, which modifies the antigen binding region by targeted mutagenesis in the variable region of the Ig genes (1). An alternative diversification mechanism prevalent in chicken and some mammals, Ig gene conversion alters the same region by targeted homologous recombination with upstream Ig pseudogenes (2).Somatic hypermutation and Ig gene conversion are related processes (3) originating from the same initial DNA lesion. The transcription-coupled deamination of cytosines by activationinduced cytidine deaminase (AID) leads to uracil that may be processed to abasic sites or strand breaks by the excision repair pathway, i.e., uracil-N-glycosylase (4, 5). The resultant DNA lesions may be repaired by mutagenesis or reco...

show abstract

The expanding polymerase universe

Cited by 152 publications

References 98 publications

DNA polymerases in adaptive immunity

DNA polymerases in adaptive immunity

The Essential C Family DnaE Polymerase Is Error-prone and Efficient at Lesion Bypass

Involvement of Rad18 in somatic hypermutation

Contact Info

Product

Resources

About