Erratum

Zewail-Foote, Maha; Li, Ven-Shun; Kohn, Harold; Bearss, David J.; Guzman, Mary; Hurley, Laurence H.

doi:10.1016/j.chembiol.2004.02.013

Cited by 14 publications

(17 citation statements)

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“…N 2 -dG adducts can arise from byproducts of an array of cellular processes, including glycolysis (14,18) and lipid peroxidation (45). In addition, there is supporting evidence that these minor groove adducts may be resistant toward excision repair (46). In this vein, the N 2 -dG adduct is the least abundant dG lesion produced from acetylaminofluorine, but it persists in tissues of animals treated with this carcinogen (47).…”

Section: Discussionmentioning

confidence: 99%

The Roles of DNA Polymerases κ and ι in the Error-free Bypass of N2-Carboxyalkyl-2′-deoxyguanosine Lesions in Mammalian Cells

Yuan

You²,

Andersen³

et al. 2011

Journal of Biological Chemistry

101

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To counteract the deleterious effects of DNA damage, cells are equipped with specialized polymerases to bypass DNA lesions. Previous biochemical studies revealed that DinB family DNA polymerases, including Escherichia coli DNA polymerase IV and human DNA polymerase , efficiently incorporate the correct nucleotide opposite some N DNA is susceptible to damage by endogenous and exogenous agents (1). To minimize cell death arising from replication blockage and mutations emanating from nucleotide misincorporation opposite the damage site, cells are equipped with several pathways to repair DNA lesions (2). Additionally, cells have evolved two major mechanisms to tolerate unrepaired DNA lesions (3), including homologous recombination and translesion synthesis (TLS) 2 (3). In this regard, synthesis past many DNA lesions requires the replacement of replicative DNA polymerases with one or a few specialized polymerases, most of which belong to the Y-family (4). Along this line, phylogenetic analysis revealed five branches of Y-family polymerases, which include UmuC, DinB, polymerase , polymerase , and REV1 (4, 5). All of these, except for UmuC, are found in eukaryotic cells (4,5). Apart from the Y-family DNA polymerases, some B-family DNA polymerases also participate in TLS. These include DNA polymerase II in Escherichia coli and polymerase , which is composed of the catalytic subunit REV3 and the regulatory subunit REV7, in eukaryotic cells (4, 5). These specialized DNA polymerases are characterized by their relatively low fidelity in replicating undamaged DNA but have the capability to bypass those DNA lesions that normally block DNA synthesis by replicative DNA polymerases (4). It was advocated that specialized DNA polymerases are evolved by nature to copy DNA base damage accurately, but they no longer bear the ability to replicate unmodified DNA with high fidelity (6). The best known example of this is the efficient and accurate bypass of cis,syn-cyclobutane pyrimidine dimers by polymerase (7,8), which is encoded by the xeroderma pigmentosum-variant gene (i.e. POLH) in humans (9). Xeroderma pigmentosum-variant patients exhibit elevated susceptibility to developing skin cancer (10). Several recent studies also demonstrated that DinB DNA polymerase, a Y-family polymerase conserved in all three kingdoms of life (11), can insert the correct dCMP opposite several N 2 -substituted guanine lesions at an efficiency that is similar to or better than opposite an unmodified guanine (12)(13)(14). The x-ray crystal structure of the catalytic core of human DNA polymerase , along with primer/template DNA and an incoming nucleotide, reveals the lack of steric hindrance in the minor groove at the primer-template junction (15), which may account for the tolerance of polymerase toward the minor groove N 2 -dG lesions. By using shuttle vector technology, we also showed that DinB (i.e. polymerase IV) is the major polymerase involved in the accurate bypass of the two diastereomers of N 2 -(1-carboxyethyl)-2Ј-deoxyguanosine (N 2 -CEdG) in ...

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Section: Discussionmentioning

confidence: 99%

The Roles of DNA Polymerases κ and ι in the Error-free Bypass of N2-Carboxyalkyl-2′-deoxyguanosine Lesions in Mammalian Cells

Yuan

You²,

Andersen³

et al. 2011

Journal of Biological Chemistry

101

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“…Increased resistance to ET-743 was also reported for yeast mutants lacking the APN1 endonuclease, which particularly is involved in base excision repair (20). The unusual effect of these repair proteins on the cytotoxicity of ET-743 has been explained by the stabilization of repair complexes by the ET adducts (1)(2)(3)(4)21). Mismatch repair status had no detectable influence on the sensitivity to ET-743 (2, 6) whereas loss of the DNA-dependent kinase (DNA-PK) was reported to sensitize cells to ET-743 (2).…”

mentioning

confidence: 90%

“…This group includes ecteinascidin-743 (ET-743, Yondelis, trabectedin), irofulven, hedamycin, and the acronycine derivative S23906. Mechanistic studies have revealed several differences in the way these compounds react with DNA-metabolizing enzymes as well as with the repair machinery (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11), which could, at least in part, explain their different activity spectra. A better understanding of the factors controlling the induction and removal of DNA damage induced by these compounds should not only facilitate their clinical application, but may also contribute to our general understanding of the structural and biological features governing adduct processing in mammalian cells.…”

mentioning

confidence: 99%

Replication and homologous recombination repair regulate DNA double-strand break formation by the antitumor alkylator ecteinascidin 743

Soares

Escargueil

Poindessous

et al. 2007

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

144

111

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Adducts induced by the antitumor alkylator ecteinascidin 743 (ET-743, Yondelis, trabectedin) represent a unique challenge to the DNA repair machinery because no pathway examined to date is able to remove the ET adducts, whereas cells deficient in nucleotide excision repair show increased resistance. We here describe the processing of the initial ET adducts into cytotoxic lesions and characterize the influence of cellular repair pathways on this process. Our findings show that exposure of proliferating mammalian cells to pharmacologically relevant concentrations of ET-743 is accompanied by rapid formation of DNA double-strand breaks (DSBs), as shown by the neutral comet assay and induction of focalized phosphorylated H2AX. The ET adducts are stable and can be converted into DSBs hours after the drug has been removed. Loss of homologous recombination repair has no influence on the initial levels of DSBs but is associated with the persistence of unrepaired DSBs after ET-743 is removed, resulting in extensive chromosomal abnormalities and pronounced sensitivity to the drug. In comparison, loss of nonhomologous end-joining had only modest effect on the sensitivity. The identification of DSB formation as a key step in the processing of ET-743 lesions represents a novel mechanism of action for the drug that is in agreement with its unusual potency. Because loss of repair proteins is common in human tumors, expression levels of selected repair factors may be useful in identifying patients particularly likely to benefit, or not, from treatment with ET-743.cancer therapy ͉ natural products ͉ lesion processing ͉ DNA repair ͉ response prediction

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“…6 Significantly, a network of hydrogen bonds has been proposed to assist in stabilizing the saframycin-ecteinascidin class of drugs in the minor groove of ds-DNA. 13,14 Therefore, it seems reasonable that perhaps other more distant structural perturbations, could possibly affect this delicate relationship and result in a drug-DNA adduct of diminished stability.…”

mentioning

confidence: 99%

Antitumor activity of tetrahydroisoquinoline analogues 3-epi-jorumycin and 3-epi-renieramycin G

Lane

Estevez²,

Mortara³

et al. 2006

Bioorganic & Medicinal Chemistry Letters

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Analogues of the tetrahydroisoquinoline family of antitumor antibiotics, 3-epi-jorumycin (3) and 3-epi-renieramycin G (4) in addition to their respective parent natural products (−)-jorumycin (1) and (−)-renieramycin G (2) were evaluated against both human colon (HCT-116) and human lung (A549) cancer cell lines. (−)-Jorumycin (1) displayed potent growth inhibition with GI 50 values in the low nanomolar range (1.9-24.3 nM), while compounds 2-4 were found to be substantially less cytotoxic (GI 50 0.6-14.0 µM).The tetrahydroisoquinoline family of alkaloids includes potent cytotoxic agents that display a range of biological properties such as antitumor and antimicrobial activities. 1 (−)-Jorumycin (1) (Figure 1), a member of the family, was isolated from the mantle and mucus of the pacific nudibranch Jorunna funebris 2 and is closely related to the saframycins, members of the renieramycin family, and, most notably, Ecteinascidin 743 (Et-743, 5) which was demonstrated to be a highly promising, exceedingly potent antitumor agent currently in phase II/III clinical trials. 3 Consistent with other members in the group, (−)-jorumycin (1) has been shown to harbor potent biological activities. 2,4 Fontana and coworkers, in the context of their original isolation studies, have demonstrated that 1 possesses activity against NIH 3T3 tumor cells (100% of inhibition at 50 ng/mL) in addition to P388, A549, HT29, and MEL28 tumor cell lines (IC 50 12.5 ng/mL). 2 Furthermore, 1 was shown to inhibit the growth of various Gram-positive bacteria (eg. Bacillus subtilis, Staphylococcus aureus) at a concentration lower than 50 ng/mL. 2 Saito and co-workers, employing (−)-jorumycin (1) prepared semisynthetically from renieramycin M, have reported potent antiproliferative activity for 1 against HCT-116 (IC 50 0.57 nM), QG56 (IC 50 0.76 nM), and DU145 (IC 50 0.49 nM) cell lines. 4 (−)-Renieramycin G (2) (Figure 1) was isolated from the marine sponge Xestospongia caycedoi by Davidson in 1992. 5 Despite having an amide carbonyl residue at C-21, 2 was reported to retain cytotoxicity against human cancer cells with MIC values of 0.5 µg/mL and 1.0 µg/mL against KB and LoVo cell lines, respectively. 5 These results are surprising in light of the fact that virtually all biologically active members of this family of tetrahydroisoquinoline alkaloids possess a carbinolamine or cyano function at C-21 that permits the formation of a potent, electrophilic iminium ion species that has been implicated

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Erratum

Cited by 14 publications

References 0 publications

The Roles of DNA Polymerases κ and ι in the Error-free Bypass of N2-Carboxyalkyl-2′-deoxyguanosine Lesions in Mammalian Cells

The Roles of DNA Polymerases κ and ι in the Error-free Bypass of N2-Carboxyalkyl-2′-deoxyguanosine Lesions in Mammalian Cells

Replication and homologous recombination repair regulate DNA double-strand break formation by the antitumor alkylator ecteinascidin 743

Antitumor activity of tetrahydroisoquinoline analogues 3-epi-jorumycin and 3-epi-renieramycin G

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