Distribution and roles of X-family DNA polymerases in eukaryotes

Uchiyama, Yosuke; Takeuchi, Ryo; Kodera, Hirofumi; Sakaguchi, Kengo

doi:10.1016/j.biochi.2008.07.005

Cited by 62 publications

(84 citation statements)

References 33 publications

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“…Pol b is a 335-amino-acid, 39-kDa polymerase encoded by the POLB locus after the splicing of its 14 constitutive exons (Uchiyama et al 2009;Yamtich and Sweasy 2009). Pol b is a member of the X-family of DNA repair polymerases, plays a key role in base excision DNA repair, and its absence leads to sensitivity to methylating agents (Yamtich and Sweasy 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Pol b is a member of the X-family of DNA repair polymerases, plays a key role in base excision DNA repair, and its absence leads to sensitivity to methylating agents (Yamtich and Sweasy 2009). POLB is believed to have evolved after the protostome-deuterostome branching, being essential in vertebrates and expressed in all cell types (Uchiyama et al 2009;Yamtich and Sweasy 2009).…”

Section: Introductionmentioning

confidence: 99%

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The adaptive significance of unproductive alternative splicing in primates

Skandalis

Frampton²,

Seger³

et al. 2010

RNA

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Alternative gene splicing is pervasive in metazoa, particularly in humans, where the majority of genes generate splice variant transcripts. Characterizing the biological significance of alternative transcripts is methodologically difficult since it is impractical to assess thousands of splice variants as to whether they actually encode proteins, whether these proteins are functional, or whether transcripts have a function independent of protein synthesis. Consequently, to elucidate the functional significance of splice variants and to investigate mechanisms underlying the fidelity of mRNA splicing, we used an indirect approach based on analyzing the evolutionary conservation of splice variants among species. Using DNA polymerase b as an indicator locus, we cloned and characterized the types and frequencies of transcripts generated in primary cell lines of five primate species. Overall, we found that in addition to the canonical DNA polymerase b transcript, there were 25 alternative transcripts generated, most containing premature terminating codons. We used a statistical method borrowed from community ecology to show that there is significant diversity and little conservation in alternative splicing patterns among species, despite high sequence similarity in the underlying genomic (exonic) sequences. However, the frequency of alternative splicing at this locus correlates well with life history parameters such as the maximal longevity of each species, indicating that the alternative splicing of unproductive splice variants may have adaptive significance, even if the specific RNA transcripts themselves have no function. These results demonstrate the validity of the phylogenetic conservation approach in elucidating the biological significance of alternative splicing.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The adaptive significance of unproductive alternative splicing in primates

Skandalis

Frampton²,

Seger³

et al. 2010

RNA

View full text Add to dashboard Cite

show abstract

“…pombe), two paralogs in a mushroom forming fungus (Coprinus cinereus), three in an echinoderm (Strongylocentrotus purpuratus), and four in vertebrates [Uchiyama et al, 2009]. The multiple paralogs within a single species are also significantly diverged, with <50% identity when comparing even the most closely related pair (Fig.…”

Section: Diversity In Pol X Members and Its Significance To Nhejmentioning

confidence: 98%

DNA polymerases in nonhomologous end joining: Are there any benefits to standing out from the crowd?

Ramsden

Asagoshi

2012

Environ and Mol Mutagen

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Chromosome breaks, often with damaged or missing DNA flanking the break site, are an important threat to genome stability. They are repaired in vertebrates primarily by nonhomologous end joining (NHEJ). NHEJ is unique among the major DNA repair pathways in that a continuous template cannot be used by DNA polymerases to instruct replacement of damaged or lost DNA. Nevertheless, at least 3 out of the 17 mammalian DNA polymerases are specifically employed by NHEJ. Biochemical and structural studies are further revealing how each of the polymerases employed by NHEJ possesses distinct and sophisticated means to overcome the barriers this pathway presents to polymerase activity. Still unclear, though, is how the resulting network of overlapping and nonoverlapping polymerase activities contributes to repair in cells. Environ. Mol. Mutagen. 53:741-751, 2012. V V C 2012 Wiley Periodicals, Inc.

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“…Nevertheless, DEMETER proteins are unusually large for this class of proteins, with unique protein domains, and they have a function beyond canonical DNA repair in excising 5mC from CG, CHG and CHH contexts (where H is A, G or T) and replacing it with unmethylated cytosine via BER (Choi et al, 2002;Gehring et al, 2006;Morales-Ruiz et al, 2006). DEMETERs are bifunctional glycosylases (Choi et al, 2002;Gong et al, 2002), and are expected to cooperate with DNA polymerase δ/ε in long-patch BER, especially because plant genomes lack sequences encoding DNA polymerase β homologs (Uchiyama et al, 2008), which are characteristic for short-patch BER. Nevertheless, some homologous plant proteins involved in short-patch BER steps (such as X-ray repair cross-complementing protein 1 (XRCC1), AP endonuclease 1 (APE1), 3'-phosphatase zinc finger DNA 3'-phosphoesterase (ZDP) and DNA ligase 1 (AtLIG1) have been identified as the components affected in DNA demethylation (Andreuzza et al, 2010;Li et al, 2015a;Li et al, 2015b).…”

Section: Dna-mediated Charge Transfermentioning

confidence: 99%

Emerging links between iron-sulfur clusters and 5-methylcytosine base excision repair in plants

Buzas

2016

Genes Genet. Syst.

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Iron-sulfur (Fe-S) clusters are ancient cofactors present in all kingdoms of life. Both the Fe-S cluster assembly machineries and target apoproteins are distributed across different subcellular compartments. The essential function of Fe-S clusters in nuclear enzymes is particularly difficult to study. The base excision repair (BER) pathway guards the integrity of DNA; enzymes from the DEMETER family of DNA glycosylases in plants are Fe-S cluster-dependent and extend the BER repertowere to excision of 5-methylcytosine (5mC). Recent studies in plants genetically link the majority of proteins from the cytosolic Fe-S cluster biogenesis (CIA) pathway with 5mC BER and DNA repair. This link can now be further explored. First, it opens new possibilities for understanding how Fe-S clusters participate in 5mC BER and related processes. I describe DNA-mediated charge transfer, an Fe-S cluster-based mechanism for locating base lesions with high efficiency, which is used by bacterial DNA glycosylases encoding Fe-S cluster binding domains that are also conserved in the DEMETER family. Second, because detailed analysis of the mutant phenotype of CIA proteins relating to 5mC BER revealed that they formed two groups, we may also gain new insights into both the composition of the Fe-S assembly pathway and the biological contexts of Fe-S proteins.

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Distribution and roles of X-family DNA polymerases in eukaryotes

Cited by 62 publications

References 33 publications

The adaptive significance of unproductive alternative splicing in primates

The adaptive significance of unproductive alternative splicing in primates

DNA polymerases in nonhomologous end joining: Are there any benefits to standing out from the crowd?

Emerging links between iron-sulfur clusters and 5-methylcytosine base excision repair in plants

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