A novel repair enzyme: UVRABC excision nuclease of Escherichia coli cuts a DNA strand on both sides of the damaged region

Sancar, Aziz; Rupp, W. Dean

doi:10.1016/0092-8674(83)90354-9

Cited by 610 publications

(381 citation statements)

References 31 publications

Supporting

Mentioning

367

Contrasting

Unclassified

Order By: Relevance

“…The nucleotide excision system controlled by the E. coli uvr system acts in a virtually non-specific manner in that it is induced to act on DNA's damaged by a wide variety of structurally unrelated damage, yet in each case the asymmetric dual incision sites are essentially invariant whether the damage is a pyrimidine dimer (3,4), an acetylaminofluorine-guanine adduct (5), a cis-platinum guanine intra-strand dimer (6) or a psoralen-thymine monoadduct (5). That these damaging agents, all producing different structural perturbations are acted upon in virtually the same manner strongly suggests that it is the UvrABC protein complex which is imposing a structure on the DNA molecule to satisfy its own substrate requirements.…”

Section: Methodsmentioning

confidence: 99%

“…These findings suggest that the enzyme mechanisms may be similar and point to the significance of studying the E. coli uvr system as a model for a DNA repair deficiency amongst patients predisposed to skin cancer The incision components of the E. coli uvr repair system responsible for the initial recognition of damaged DNA consists of the UvrA protein which in the presence of ATP binds to the damaged DNA, as well as to undamaged DNA duplexes (2). The UvrA protein requires thesimultaneous presence of the UvrB and UvrC proteins to initiate a dual incision event in DNAs containing ultraviolet light induced pyrimidine dimers (3,4) and 6,4-pyrimidine-pyrimidone adducts (3), photoactivated psoralen mono-and diadducts (5), acetylaminofluorine-guanine adducts (5), cis-platinum-guanine adducts (6) and benzo [a]pyrene-guanine adducts (7). In almost all of those experiments carried out with DNA substrates of defined sequences, the dual incision events were shown to involve a 5'-incision event 7 nucleotides to a damaged site and 3-4 nucleotides 3'-to the same site.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The effect ofEscherichia coliUvr protein binding on the topology of supercoiled DNA

Grossman

1986

Nucl Acids Res

View full text Add to dashboard Cite

The effects of the binding of the E. coli UvrA and UvrB proteins on the linking number (AL) of superhelical DNA has been measured. The effects of cofactor ATP structure on UvrAB-nucleoprotein complex formation revealed that nucleotide binding, not hydrolysis; is sufficient to locally unwind the DNA helix of both ultraviolet light-damaged as well as undamaged DNAs. The extent of this unwinding is of the same order of magnitude as the nucleotide distances of the double incision sites generated by the UvrABC endonucleolytic reaction. INTRODUCTIONThe E. coli uvr repair system is unique in that its specificity is sufficiently broad to accommodate a wide spectrum of seemingly different kinds of DNA damaging agents. As a consequence, organisms possessing such a system can respond to a plethora of environmental hazards without having to evolve new enzyme systems as new types of agents are introduced into its environment. Parenthetically, the spectrum of agents to which E. coli uvr mutants are sensitive is remarkably similar to the damage sensitivity of human repair-deficient skin fibroblasts derived from xeroderma pigmentosum patients (1). These findings suggest that the enzyme mechanisms may be similar and point to the significance of studying the E. coli uvr system as a model for a DNA repair deficiency amongst patients predisposed to skin cancer The incision components of the E. coli uvr repair system responsible for the initial recognition of damaged DNA consists of the UvrA protein which in the presence of ATP binds to the damaged DNA, as well as to undamaged DNA duplexes (2). The UvrA protein requires thesimultaneous presence of the UvrB and UvrC proteins to initiate a dual incision event in DNAs containing ultraviolet light induced pyrimidine dimers (3,4) and 6,4-pyrimidine-pyrimidone adducts (3), photoactivated psoralen mono-and diadducts (5), acetylaminofluorine-guanine adducts (5), cis-platinum-guanine adducts (6) and benzo[a]pyrene-guanine adducts (7). In almost all of those experiments carried out with DNA substrates of defined sequences, the dual incision events were shown to involve a 5'-incision event 7 nucleotides to a damaged site and 3-4 nucleotides 3'-to the same site. In spite of the fact that the primary chemical events are dissimilar and the extent to which these agents distort DNA, the sites of incision are

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The effect ofEscherichia coliUvr protein binding on the topology of supercoiled DNA

Grossman

1986

Nucl Acids Res

View full text Add to dashboard Cite

show abstract

“…In this study, we focused on an NER enzyme, the E. coli UvrABC nuclease. The NER enzyme is involved in the elimination of bulky DNA lesions, such as the cyclobutane thymine dimer and the (6-4) thymine [(6-4)TT] dimer [18][19][20]. In addition, it removes some forms of oxidative damage, such as an abasic (AP) site and thymine glycol, from DNA [21].…”

Section: Introductionmentioning

confidence: 99%

UvrA and UvrB enhance mutations induced by oxidized deoxyribonucleotides

et al. 2007

View full text Add to dashboard Cite

Oxidatively damaged DNA precursors (deoxyribonucleotides) are formed by reactive oxygen species. After the damaged DNA precursors are incorporated into DNA, they might be removed by DNA repair enzymes. In this study, to examine whether a nucleotide excision repair enzyme, Escherichia coli UvrABC, could suppress the mutations induced by oxidized deoxyribonucleotides in vivo, oxidized DNA precursors, 8-hydroxy-2´-deoxyguanosine 5´-triphosphate and 2-hydroxy-2´-deoxyadenosine 5´-triphosphate, were introduced into uvrA, uvrB, and uvrC E. coli strains, and mutations in the chromosomal rpoB gene were analyzed. Unexpectedly, these oxidized DNA precursors induced mutations only slightly in the uvrA and uvrB strains. In contrast, effect of the uvrC-deficiency was not observed. Next, mutT, mutT/uvrA, and mutT/uvrB E. coli strains were treated with H 2 O 2 , and the rpoB mutant frequencies were calculated. The frequency of the H 2 O 2 -induced mutations was increased in all of the strains tested; however, the increase was threeto four-fold lower in the mutT/uvrA and mutT/uvrB strains than in the mutT strain. Thus, UvrA and UvrB are involved in the enhancement, but not in the suppression, of the mutations induced by these oxidized deoxyribonucleotides. These results suggest a novel role for UvrA and UvrB in the processing of oxidative damage.

show abstract

“…The reaction mixture (5 Similarly, UvrD protein showed no effect on the incorporation when the substrate DNA was non-irradiated, even in the presence of UvrABC enzyme (data not shown). Figure 2 shows the time-course of the reaction in the presence and absence of UvrD protein.…”

Section: Polyacrylamide Gel Analysis Of Products Of the Incision Reacmentioning

confidence: 99%

“…The products of these genes are components of an enzyme that induces strand breaks at both sides of a pyrimidine dimer, thereby releasing a damaged portion of nucleotides from the DNA (4,5).…”

Section: Introductionmentioning

confidence: 99%

Stimulation of the UvrABC enzyme-catalyzed repair reactions by the UvrD protein (DNA helicase II)

Kumura¹,

Sekiguchi²,

Stemum

et al. 1985

Nucl Acids Res

View full text Add to dashboard Cite

show abstract

A novel repair enzyme: UVRABC excision nuclease of Escherichia coli cuts a DNA strand on both sides of the damaged region

Cited by 610 publications

References 31 publications

The effect ofEscherichia coliUvr protein binding on the topology of supercoiled DNA

The effect ofEscherichia coliUvr protein binding on the topology of supercoiled DNA

UvrA and UvrB enhance mutations induced by oxidized deoxyribonucleotides

Stimulation of the UvrABC enzyme-catalyzed repair reactions by the UvrD protein (DNA helicase II)

Contact Info

Product

Resources

About