HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 52, 49283-49288, December 28, 2001

This Article Abstract Full Text (PDF) All Versions of this Article: 276/52/49283    most recent M107779200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kuraoka, I. Articles by Lindahl, T. Search for Related Content PubMed PubMed Citation Articles by Kuraoka, I. Articles by Lindahl, T.

Oxygen Free Radical Damage to DNA

TRANSLESION SYNTHESIS BY HUMAN DNA POLYMERASE  AND RESISTANCE TO EXONUCLEASE ACTION AT CYCLOPURINE DEOXYNUCLEOSIDE RESIDUES^*

Isao Kuraoka^§, Peter Robins, Chikahide Masutani^¶, Fumio Hanaoka^¶, Didier Gasparutto, Jean Cadet, Richard D. Wood^**, and Tomas Lindahl

From the  Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, Hertfordshire EN6 3LD, United Kingdom, the ^¶ Institute of Molecular and Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan, and the  Laboratoire des Lésions des Acides Nucléiques, Service de Chimie Inorganique et Biologique and UMR 5046, Département de Recherche Fondamentale sur la Matière Condensée, Commissariat á l'Energie Atomique, F-38054 Grenoble Cedex 9, France

Received for publication, August 13, 2001, and in revised form, October 1, 2001

	ABSTRACT

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS DISCUSSION REFERENCES

Cyclopurine deoxynucleosides are common DNA lesions generated by exposure to reactive oxygen species under hypoxic conditions. The S and R diastereoisomers of cyclodeoxyadenosine on DNA were investigated separately for their ability to block 3' to 5' exonucleases. The mammalian DNA-editing enzyme DNase III (TREX1) was blocked by both diastereoisomers, whereas only the S diastereoisomer was highly efficient in preventing digestion by the exonuclease function of T4 DNA polymerase. Digestion in both cases was frequently blocked one residue before the modified base. Oligodeoxyribonucleotides containing a cyclodeoxyadenosine residue were further employed as templates for synthesis by human DNA polymerase  (pol ). pol  could catalyze translesion synthesis on the R diastereoisomer of cyclodeoxyadenosine. On the S diastereoisomer, pol  could catalyze the incorporation of one nucleotide opposite the lesion but could not continue elongation. Although pol  preferentially incorporated dAMP opposite the R diastereoisomer, elongation continued only when dTMP was incorporated, suggesting bypass of this lesion by pol  with reasonable fidelity. With the S diastereoisomer, pol  mainly incorporated dAMP or dTMP opposite the lesion but could not elongate even after incorporating a correct nucleotide. These data suggest that the S diastereoisomer may be a more cytotoxic DNA lesion than the R diastereoisomer.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS DISCUSSION REFERENCES

More than 30 different base lesions have been characterized in DNA after exposure to reactive oxygen species (1, 2). Many of these are ring-saturated or ring-condensed derivatives of pyrimidines. However, oxidation of purines also occurs, in particular in association with saturation or fragmentation of the imidazole ring of guanine. These lesions are generally removed by specialized DNA glycosylases called Nth and Fpg in Escherichia coli, and NTH1 and OGG1 in human cells (3).

A structurally unusual form of lesion generated by hydroxyl radicals is a cyclopurine deoxynucleoside (cyPu).¹ These are increasingly recognized as significant, chemically stable lesions after exposure of cells or DNA solutions to oxygen free radicals, with cyclodeoxyadenosine being formed slightly more frequently than cyclodeoxyguanosine (4, 5). A covalent bond is formed between the C-8 position of the purine and the C-5' residue of the adjacent deoxyribose. Consequently, the base is attached to the DNA backbone by two covalent bonds, one of which is the normal glycosyl bond. After -irradiation of a neutral DNA solution under N₂O, 8,5'-cyclo-2'-deoxyadenosine was generated at a 10-fold lower yield that the major lesions 8-oxo-7,8-dihydroguanine or thymine glycol (6). The cyPu lesions have recently been shown to be corrected by nucleotide excision repair (NER) rather than by a process related to base excision repair or direct damage reversal (7, 8). Thus, the main mode of repair for this form of oxidative DNA damage is different from that of the great majority of oxidative base lesions.

A cyPu can occur in two stereoisomeric forms, 5'R and 5'S (Fig. 1). Oxygen free radicals generate the 5'S and 5'R isomers in similar amounts in double-stranded DNA, whereas the 5'R diastereoisomer is predominant in single-stranded DNA (1, 2, 4). Until recently, synthesis of oligodeoxyribonucleotides containing these adducts has been technically difficult, in particular with regard to the R diastereoisomer (9, 10). Because both cyPu lesions inhibit DNA synthesis by replicative mammalian and microbial DNA polymerases (7), and the S isomer of cyPu blocks gene expression (8), these lesions would have a potentially cytotoxic effect.

Here, we have evaluated the susceptibility of oligonucleotides containing this lesion in either of its diastereoisomeric forms to several 3' exonucleases. The results suggest that stereospecific differences between R- and S-cyPu residues affect the exonucleolytic activity. Oligonucleotides with either a single R- or S-cyPu residue were further tested as substrates for translesion synthesis by human polymerase  (pol ). Human pol  is the product of the XPV gene, which is mutated in a cancer-prone genetic disorder, xeroderma pigmentosum variant (11, 12). The enzyme can catalyze efficient and accurate translesion synthesis opposite lesions such as a cyclobutane thymine dimer generated by UV irradiation (11, 12) and 8-oxo-7,8-dihydroguanine generated by hydroxyl radicals (13). We find that stereospecific differences between R- and S-cyPu residues also affect translesion synthesis, with the S-cyPu much less efficiently bypassed. As reported previously (7), the S diastereoisomer is removed by NER even less efficiently than the R isomer. The present data provide additional reasons why the S diastereoisomer might be more of a challenge to cell survival than the R diastereoisomer in vivo.

	EXPERIMENTAL PROCEDURES

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS DISCUSSION REFERENCES

Oligodeoxyribonucleotides Containing a Site-specific Purine Cyclodeoxynucleoside Residue-- Oligodeoxyribonucleotides with either a (5'R)-5',8-cyclo-2'-deoxyadenosine (5'R-cyclo-dA) or (5'S)-5',8-cyclo-2'-deoxyadenosine residue (5'S-cyclo-dA) were prepared using modified phosphoramidite chemistry as described (9, 10). The lesions were incorporated into the sequence 5'-CACTTCGGXTCGTGACTGATCT-3', where X is 5'R-cyclo-dA or 5'S-cyclo-dA. The oligonucleotides were 5'-phosphorylated using [-³²P]ATP (Amersham Biosciences, Inc.) and T4 polynucleotide kinase (New England Biolabs) and then purified on a denaturing 16% polyacrylamide gel. Double-stranded DNA substrates for exonucleases were prepared by annealing with a complementary strand of sequence 5'-AGATCAGTCACGATCCGAAGTG-3'.

Nuclease Assays-- Mammalian DNase III (TREX1), which is a major nuclear DNA-specific 3' exonuclease with properties of an editing factor, was purified from cell nuclei as described (14). T4 DNA polymerase, which has a 3' exonucleolytic function, was obtained from New England Biolabs.

For 3' exonucleolytic digestion, 5'-³²P end-labeled oligonucleotides containing either a 5'R-cyclo-dA or 5'S-cyclo-dA residue or control oligonucleotides without a lesion were incubated with different amounts of exonucleases as indicated in the figure legends. T4 DNA polymerase was assayed in 10-µl reaction mixtures containing 50 mM NaCl, 10 mM Tris-HCl (pH 7.9), 10 mM MgCl₂, and 1 mM dithiothreitol at 37 °C for 30 min. For mammalian DNase III assays, 10-µl reaction mixtures containing 50 mM Tris-HCl (pH 7.5), 4 mM MgCl₂, 1 mM dithiothreitol, and 100 µl/ml bovine serum albumin were used, and incubations were at 37 °C for 30 min. Reactions were terminated by the addition of 8 µl of stop solution containing 95% formamide, 20 mM EDTA, 0.025% bromphenol blue, and 0.025% xylene cyanol. Oligonucleotide fragments were separated by electrophoresis on a denaturing 16% polyacrylamide gel, dried, and exposed to x-ray film (Kodak Bio-Max) or a PhosphorImager screen (Molecular Dynamics).

Translesion Synthesis Assays-- The 5'-³²P-labeled primer-template DNA was prepared by mixing a 13-mer (Fig. 3A) or 14-mer (Fig. 4, C and D) primer labeled at its 5' end with a 22-mer oligonucleotide containing either a 5'R-cyclo-dA or a 5'S-cyclo-dA residue at a molar ratio of 1:1. Reaction mixtures of 5 µl contained 40 mM Tris-HCl (pH 8.0), 1 mM MgCl₂, the four dNTPs at 100 µM each, 10 mM dithiothreitol, 250 µl/ml bovine serum albumin, 60 mM KCl, 2.5% glycerol, and 40 nM of the 5'-³²P-labeled primer-template DNA were incubated at 37 °C for 15 min. Reactions were terminated by the addition of 8 µl of stop solution. Products were separated by electrophoresis on a denaturing 16% polyacrylamide gel, dried, and exposed as described above.

	RESULTS

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS DISCUSSION REFERENCES

Structure of cyPu-- A model indicating how the R and S diastereoisomers arise from 8,5'-cyclodeoxyadenosine is shown in Fig. 1. Molecular mechanics calculations predict that the deoxyribose moiety is anomalously puckered, a distortion required to form the C(5')-C (8) bond (15). The attendant changes in DNA conformation would greatly weaken base pairing with a complementary residue in the double helix (15). The distorted structure of the lesion is consistent with its ability to block DNA replication and transcription (7, 8).

View larger version (19K): [in this window] [in a new window]   Fig. 1.   The 5'R and 5'S diastereoisomers of 5',8-cyclodeoxyadenosine. The diagram at the top indicates the proximity of the H-8 of adenine to two hydrogens on the C-5' of deoxyribose. In DNA, oxygen free radicals can promote loss of the hydrogen labeled pro-R, leading to the 5'R diastereoisomer at the lower left or loss of the hydrogen labeled pro-S, leading to the 5'S diastereoisomer at the lower right. Unusual sugar puckering (not shown here) arises as a consequence of the close proximity of the 8 and 5' positions in the cyclized adduct (15).

Exonucleolytic Activity on cyPu Residues-- Distinct structural distortions of DNA caused by the two diastereoisomers of cyPu residues could be detected in principle by the relative sensitivities of the lesions to exonucleolytic digestion. To investigate this point, oligonucleotides containing a site-specific cyPu residue were incubated with T4 DNA polymerase, which functions as a processive 3' to 5' exonuclease in the absence of deoxynucleoside triphosphates. This enzyme has been used previously to detect bulky DNA lesions such as UV photoproducts, psoralen interstrand cross-links, and cisplatin adducts. Exonucleolytic activity is typically blocked 1-3 nucleotides from the site of bulky DNA damage (16, 17). Fig. 2B shows that the exonucleolytic activity of T4 DNA polymerase is strongly inhibited one nucleotide from 5'S-cyclo-dA as indicated by the accumulation of a 10-mer even after attempted digestion at high enzyme concentrations. In contrast, the oligonucleotide containing 5'R-cyclo-dA could be cleaved to mononucleotides, although the lesion functioned as a pause site that partly blocked exonuclease activity, as seen at lower enzyme concentrations (Fig. 2B, lanes 6-10). These results demonstrate that stereospecific differences between the 5'R- and 5'S-cyclo-dA residues differently affect the exonucleolytic action of T4 DNA polymerase. It is interesting that the 5'S diastereoisomer was a much stronger block to exonucleolytic degradation by T4 DNA polymerase than the 5'R analogue, although the R form was a better NER substrate than the S form (7).

View larger version (41K): [in this window] [in a new window]   Fig. 2.   Partial resistance to exonucleases. A, schematic drawing of 22-mer oligonucleotide containing a cyPu residue. The positions of partly or fully blocked digestion by 3' exonuclease activity are indicated. B, action of the exonuclease function of T4 DNA polymerase on an oligonucleotide containing a purine cyclodeoxynucleoside. Control oligonucleotide (lanes 1-5), 5'R-cyclodeoxyadenosine-containing oligonucleotide (lanes 6-10), and 5'S-cyclodeoxyadenosine-containing oligonucleotide (lanes 11-15) were digested with increasing amounts of T4 DNA polymerase (0.3, 0.75, 1.5, and 3 units) in the absence of deoxynucleoside triphosphates at 37 °C for 30 min. C, action of the exonuclease function of mammalian DNase III on an oligonucleotide containing a purine cyclodeoxynucleoside. A control oligonucleotide (lanes 1-5), a 5'R-cyclodeoxyadenosine-containing oligonucleotide (lanes 6-10), and a 5'S-cyclodeoxyadenosine-containing oligonucleotide (lanes 11-15) were digested with increasing amounts of DNase III (25, 50, 100, and 150 fmol) at 37 °C for 30 min.

The mammalian nuclear 3' to 5' exonuclease DNase III/TREX1 can remove a mismatched nucleotide residue from the 3' terminus of double-stranded DNA and effectively digests nondamaged single-stranded DNA (14, 18). This enzyme has sequence homology with the proofreading DnaQ protein of the E. coli pol III holoenzyme as well as with the 3' exonuclease domain of eukaryotic DNA polymerase , and has biochemical properties consistent with a role in DNA editing. Fig. 2C shows that the exonucleolytic activity of DNase III was strongly blocked by both 5'R- and 5'S-cyclo-dA (lanes 6-15), whereas oligonucleotides without a lesion were completely digested (lanes 1-5). The strong block to DNase III digestion by a 5'R-cyclo-dA residue was in contrast to the results obtained with T4 DNA polymerase (Fig. 2B, lanes 6-10). The predominant digestion product of 5'R-cyclo-dA by DNase III was a 9-mer, whereas that of 5'S-cyclo-dA was a 10-mer at the same enzyme concentration. These observations also indicated that stereospecific differences between 5'R- and 5'S-cyclo-dA residues differently affect the exonucleolytic action of DNase III.

In additional experiments, oligonucleotides with a cyPu residue were incubated with the 3' to 5' exonuclease activity of E. coli exonuclease III, snake venom phosphodiesterase, or nuclease P1 in similar assays. A small region adjacent to the cyPu lesion was apparently protected from digestion by these enzymes, indicating that cyPu residues in monomeric form could not be released (data not shown). However, we did not detect stereospecific differences between digestion of 5'R- and 5'S-cyclo-dA residues with these enzymes.

Translesion Synthesis on cyPu Residues-- To examine whether pol  had translesion synthesis activity at cyPu residues, a 22-mer oligonucleotide containing a single lesion was employed as template and annealed to a 5'-³²P-labeled 13-mer oligonucleotide (Fig. 3A). The latter served as a primer and was positioned so that the first nucleotide was incorporated opposite a single 5'R- or 5'S-cyclo-dA residue. T7 DNA polymerase (T7 pol), and pol  could synthesize DNA products of up to 22 nucleotides in length on the control template (Fig. 3B, lanes 1-6). Under these conditions, synthesis increased linearly up to 1.2 fmol of pol , suggesting that the enzyme catalyzed synthesis without recycling. As reported previously (11, 12), pol  is able to bypass UV-induced cyclobutane pyrimidine dimers, similar to related translesion polymerases such as E. coli pol V (umuD'₂·C complex) (19, 20) and yeast pol  (21). When the template DNA contained a 5'R-cyclo-dA residue, pol  could catalyze some translesion synthesis at higher enzyme concentrations (Fig. 3B, lanes 8-12). On the other hand, using template DNA with a 5'S-cyclo-dA residue, pol  incorporated one nucleotide opposite the single lesion in reactions with a high enzyme concentration, but bypass products were hardly detected (Fig. 3B, lanes 14-18). T7 pol could incorporate one nucleotide opposite either 5'R- or 5'S-cyclo-dA residues (Fig. 3B, lanes 7 and 13) as reported (7). From these results, we conclude that human pol  has the ability to bypass a 5'R-cyclo-dA residue with only weak activity on the 5'S diastereoisomer.

View larger version (62K): [in this window] [in a new window]   Fig. 3.   Translesion synthesis by human pol . A, DNA template for the lesion bypass DNA polymerase assay. A 13-mer primer was 5'-labeled with 32P and annealed with the 22-mer oligonucleotide containing the lesion. The position of control-dA, 5'R-cyclo-dA, or 5'S-cyclo-dA in the DNA is indicated in bold. B, Lanes 1, 7, and 13 contained 0.1 units of T7 polymerase. Control-dA (lanes 1-6), 5'R-cyclo-dA (lanes 7-12), and 5'S-cyclo-dA (lanes 13-18) in the DNA template were incubated with increasing amounts of pol  (0, 0.1, 0.2, 0.4, and 1.2 fmol) at 37 °C for 30 min.

To examine the nucleotide preference for incorporation opposite a lesion by pol , polymerization reactions were performed in the presence of only a single deoxynucleotide (Fig. 4A). Pol  replicates undamaged DNA with low fidelity (22). As reported previously (11), pol  stops synthesis after incorporating an incorrect nucleotide even on undamaged templates. This activity was observed on our control template (Fig. 4B, lanes 4-7). When A was the template nucleotide, dTTP was incorporated more than other nucleotides. On a template containing a 5'R-cyclo-dA residue, pol  instead preferred to incorporate dATP but could also incorporate the other three nucleotides to some extent (Fig. 4B, lanes 11-14). On the other hand, using a template containing a 5'S-cyclo-dA residue, pol  preferentially incorporated either dAMP or dTMP opposite the lesion (Fig. 4B, lanes 18-21). For lesion bypass, nucleotides must be incorporated beyond the lesion after the initial incorporation (in this case, "incorrect" dAMP or "correct" dTMP) opposite the lesion. To test this model, we designed two sets of 14-mer primers that had two different sequences at their 3' ends, to determine which sequence allowed pol  to elongate past the lesion. When the 14-mer primer had the sequence A opposite a control dA, 5'R-, or 5'S-cyclo-dA, pol  could not continue synthesis of DNA chains from a primer terminus (Fig. 4C, lanes 2-4). These data indicate that pol  stopped DNA synthesis after incorporating one dAMP opposite the lesion. On a primer containing the sequence T (the correct nucleotide), pol  could elongate DNA chains on the control-dA or 5'R-cyclo-dA but only inefficiently on the 5'S-cyclo-dA (Fig. 4D).

View larger version (56K): [in this window] [in a new window]   Fig. 4.   Nucleotide selectivity of pol  incorporation opposite a cyPu lesion. A, schematic drawing of a 22-mer oligonucleotide with the lesion, annealed to a 32P-labeled primer. B, Pol  was incubated with template DNA in the presence of all four dNTPs (lanes 3, 10, and 17), with one of the indicated dNTPs (lanes 4-7, 11-14, and 18-21), or in the absence of dNTPs (lanes 2, 9, and 16). C and D, ability of pol  (1 fmol) to elongate DNA chains past the cyPu lesion. 32P-labeled 14-mer primer contained a terminal A (panel C) or T (panel D) at the 3' end and was annealed to a 22-mer oligonucleotide with control-dA (lane 2), 5'R-cyclo-dA (lane 3), or 5'S-cyclo-dA (lane 4) or without 22-mer oligonucleotide (lane 1).

	DISCUSSION

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS DISCUSSION REFERENCES

The cyPu lesions generated by reactive oxygen species potentially have a cytotoxic effect by inhibiting DNA replication and transcription. Such lesions in DNA can be removed by the nucleotide excision-repair (NER) machinery, albeit inefficiently, but not by the base excision-repair machinery and not by a direct reversal reaction in human cells (7, 8).

In this study, we have found that stereospecific differences between the 5'R- and 5'S-cyclo-dA residues affect the relative resistance to exonucleolytic activity (Fig. 2) and give rise to different efficiencies of translesion synthesis by pol  (Figs. 3 and 4). We noted differences previously in the efficiency of the human NER pathway to remove the 5'R- and 5'S-cyclo-dA lesions from double-stranded DNA. The S diastereoisomer was less efficiently removed by NER than the R isomer in human cells. These and current data are summarized in Table I. Oxygen free radicals generate the 5'S and 5'R isomer in similar amounts in duplex DNA (1, 2, 4). Because the S diastereoisomer is less efficiently repaired and, as shown here, is also less efficiently bypassed by pol , the S diastereoisomer is likely to be a more highly cytotoxic DNA lesion than the R diastereoisomer in vivo.

View this table: [in this window] [in a new window]   Table I Summary of NER efficiency, translesion synthesis by pol , and resistance to exonuclease action at cyPu residues

To bypass the 5'S diastereoisomer, human cells might need another polymerase or co-factor in addition to pol . Such error-prone bypass reactions could result in mutations caused by cyPu residues. By comparison, it has been reported that yeast pol  stops DNA synthesis after incorporating one dCMP opposite an AAF-G and either dGMP or dAMP opposite an apurinic/apyrimidinic site (23) and that yeast pol  can then extend DNA synthesis past the AP site. Another group (24) reported that human pol  (hRad30B) incorporated one nucleotide opposite a (6-4) T-T photoproduct but that the enzyme was unable to extend DNA synthesis past the lesion. Yeast pol  could extend this product. In E. coli, RecA protein efficiently stimulates lesion bypass by pol V (23).

Because cyPu lesions seem to be removed only by the nucleotide excision repair system in vivo, NER-defective xeroderma pigmentosum patients may accumulate this stable chemical lesion in the DNA of nonregenerating cells over long periods of time, because of endogenous oxidative damage. Lesion accumulation could also be fostered in dividing cells by translesion polymerases such as pol  and pol . Because cyPu lesions potentially could inhibit both DNA replication and transcription (8), the lesions would be a challenge to maintenance of cell viability. Such lesion accumulation could be a cause of the slow but progressive neural degeneration observed in xeroderma pigmentosum patients who are protected from sun exposure (7, 8).

Randerath and co-workers used a sensitive ³²P-postlabeling method to detect small amounts of indigenous altered nucleotides, called I compounds, in enzymatic hydrolysates of DNA from mammalian cells (for review, see Ref. 25). The chemical nature of the various I compounds, each of which is typically present at a level of 5-200 residues/mammalian genome, have remained unknown. However, several major I compounds that were particularly abundant after cellular oxidative stress have been identified recently, as dinucleotides containing a 8,5'-cyclo-2'-deoxyadenosine moiety (26). These finding provide strong evidence that cyPu residues are highly relevant oxidative lesions in mammalian DNA. They are presumably generated continuously by oxidative stress and then are slowly removed by nucleotide excision repair, so that a steady state level of the lesion is observed in vivo.

	ACKNOWLEDGEMENTS

We thank Drs. John Essigmann, Kaushik Mitra, and Paul Henderson (Massachusetts Institute of Technology) for discussions and Kaushik Mitra for drawing Fig. 1.

	FOOTNOTES

^* This work was supported by the Imperial Cancer Research Fund and by grants from the French Atomic Energy Commission and the Comité de Radioprotection d'Electricité de France (to J. C.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^§ Recipient of a postdoctoral fellowship from the Japan Society for the Promotion of Science. Present address: Institute of Molecular and Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565-0871, Japan.

^** To whom correspondence should be addressed: University of Pittsburgh Cancer Institute, S867 Scaife Hall, Box 100, Pittsburgh, PA 15261. Tel.: 412-648-9248; Fax: 412-383-9822; E-mail: rdwood@pitt.edu.

Published, JBC Papers in Press, October 24, 2001, DOI 10.1074/jbc.M107779200

	ABBREVIATIONS

The abbreviations used are: cyPu, cyclopurine 2'-deoxynucleoside; 5'R-cyclo-dA, (5'R)-5',8-cyclo-2'-deoxyadenosine; 5'S-cyclo-dA, (5'S)-5',8-cyclo-2'-deoxyadenosine; T7 pol, T7 DNA polymerase; pol , DNA polymerase ; NER, nucleotide excision repair.

	REFERENCES

TOP ABSTRACT INTRODUCTION EXPERIMENTAL PROCEDURES RESULTS DISCUSSION REFERENCES

This article has been cited by other articles:

				R. R. Laposa, E. J. Huang, and J. E. Cleaver Increased apoptosis, p53 up-regulation, and cerebellar neuronal degeneration in repair-deficient Cockayne syndrome mice PNAS, January 23, 2007; 104(4): 1389 - 1394. [Abstract] [Full Text] [PDF]

				P. Jaruga, J. Theruvathu, M. Dizdaroglu, and P. J. Brooks Complete release of (5'S)-8,5'-cyclo-2'-deoxyadenosine from dinucleotides, oligodeoxynucleotides and DNA, and direct comparison of its levels in cellular DNA with other oxidatively induced DNA lesions Nucleic Acids Res., June 23, 2004; 32(11): e87 - e87. [Abstract] [Full Text] [PDF]

				I. G. Minko, M. T. Washington, M. Kanuri, L. Prakash, S. Prakash, and R. S. Lloyd Translesion Synthesis past Acrolein-derived DNA Adduct, gamma -Hydroxypropanodeoxyguanosine, by Yeast and Human DNA Polymerase eta J. Biol. Chem., January 3, 2003; 278(2): 784 - 790. [Abstract] [Full Text] [PDF]

				R. J. Kokoska, K. Bebenek, F. Boudsocq, R. Woodgate, and T. A. Kunkel Low Fidelity DNA Synthesis by a Y Family DNA Polymerase Due to Misalignment in the Active Site J. Biol. Chem., May 24, 2002; 277(22): 19633 - 19638. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) All Versions of this Article: 276/52/49283    most recent M107779200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kuraoka, I. Articles by Lindahl, T. Search for Related Content PubMed PubMed Citation Articles by Kuraoka, I. Articles by Lindahl, T.