hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup

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Standard

hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup. / Kavli, Bodil; Sundheim, Ottar; Akbari, Mansour; Otterlei, Marit; Nilsen, Hilde; Skorpen, Frank; Aas, Per Arne; Hagen, Lars; Krokan, Hans E; Slupphaug, Geir.

I: The Journal of Biological Chemistry, Bind 277, Nr. 42, 18.10.2002, s. 39926-36.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Kavli, B, Sundheim, O, Akbari, M, Otterlei, M, Nilsen, H, Skorpen, F, Aas, PA, Hagen, L, Krokan, HE & Slupphaug, G 2002, 'hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup', The Journal of Biological Chemistry, bind 277, nr. 42, s. 39926-36. https://doi.org/10.1074/jbc.M207107200

APA

Kavli, B., Sundheim, O., Akbari, M., Otterlei, M., Nilsen, H., Skorpen, F., Aas, P. A., Hagen, L., Krokan, H. E., & Slupphaug, G. (2002). hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup. The Journal of Biological Chemistry, 277(42), 39926-36. https://doi.org/10.1074/jbc.M207107200

Vancouver

Kavli B, Sundheim O, Akbari M, Otterlei M, Nilsen H, Skorpen F o.a. hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup. The Journal of Biological Chemistry. 2002 okt. 18;277(42):39926-36. https://doi.org/10.1074/jbc.M207107200

Author

Kavli, Bodil ; Sundheim, Ottar ; Akbari, Mansour ; Otterlei, Marit ; Nilsen, Hilde ; Skorpen, Frank ; Aas, Per Arne ; Hagen, Lars ; Krokan, Hans E ; Slupphaug, Geir. / hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup. I: The Journal of Biological Chemistry. 2002 ; Bind 277, Nr. 42. s. 39926-36.

Bibtex

@article{54949c0bf0da496093beb92fd3b580c4,
title = "hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup",
abstract = "hUNG2 and hSMUG1 are the only known glycosylases that may remove uracil from both double- and single-stranded DNA in nuclear chromatin, but their relative contribution to base excision repair remains elusive. The present study demonstrates that both enzymes are strongly stimulated by physiological concentrations of Mg2+, at which the activity of hUNG2 is 2-3 orders of magnitude higher than of hSMUG1. Moreover, Mg2+ increases the preference of hUNG2 toward uracil in ssDNA nearly 40-fold. APE1 has a strong stimulatory effect on hSMUG1 against dsU, apparently because of enhanced dissociation of hSMUG1 from AP sites in dsDNA. hSMUG1 also has a broader substrate specificity than hUNG2, including 5-hydroxymethyluracil and 3,N(4)-ethenocytosine. hUNG2 is excluded from, whereas hSMUG1 accumulates in, nucleoli in living cells. In contrast, only hUNG2 accumulates in replication foci in the S-phase. hUNG2 in nuclear extracts initiates base excision repair of plasmids containing either U:A and U:G in vitro. Moreover, an additional but delayed repair of the U:G plasmid is observed that is not inhibited by neutralizing antibodies against hUNG2 or hSMUG1. We propose a model in which hUNG2 is responsible for both prereplicative removal of deaminated cytosine and postreplicative removal of misincorporated uracil at the replication fork. We also provide evidence that hUNG2 is the major enzyme for removal of deaminated cytosine outside of replication foci, with hSMUG1 acting as a broad specificity backup.",
keywords = "Animals, Binding Sites, Cattle, Cell Cycle, Cell Nucleus/metabolism, Chromatin/metabolism, Cloning, Molecular, DNA Glycosylases, DNA Repair, DNA, Single-Stranded/chemistry, Dose-Response Relationship, Drug, HeLa Cells, Humans, Immunoglobulin G/metabolism, Kinetics, Magnesium Chloride/pharmacology, Microscopy, Fluorescence, Models, Biological, N-Glycosyl Hydrolases/chemistry, Polymerase Chain Reaction, Promoter Regions, Genetic, Protein Binding, Recombinant Proteins/metabolism, Salts/pharmacology, Substrate Specificity, Tumor Cells, Cultured, Uracil/chemistry, Uracil-DNA Glycosidase",
author = "Bodil Kavli and Ottar Sundheim and Mansour Akbari and Marit Otterlei and Hilde Nilsen and Frank Skorpen and Aas, {Per Arne} and Lars Hagen and Krokan, {Hans E} and Geir Slupphaug",
year = "2002",
month = oct,
day = "18",
doi = "10.1074/jbc.M207107200",
language = "English",
volume = "277",
pages = "39926--36",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "42",

}

RIS

TY - JOUR

T1 - hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup

AU - Kavli, Bodil

AU - Sundheim, Ottar

AU - Akbari, Mansour

AU - Otterlei, Marit

AU - Nilsen, Hilde

AU - Skorpen, Frank

AU - Aas, Per Arne

AU - Hagen, Lars

AU - Krokan, Hans E

AU - Slupphaug, Geir

PY - 2002/10/18

Y1 - 2002/10/18

N2 - hUNG2 and hSMUG1 are the only known glycosylases that may remove uracil from both double- and single-stranded DNA in nuclear chromatin, but their relative contribution to base excision repair remains elusive. The present study demonstrates that both enzymes are strongly stimulated by physiological concentrations of Mg2+, at which the activity of hUNG2 is 2-3 orders of magnitude higher than of hSMUG1. Moreover, Mg2+ increases the preference of hUNG2 toward uracil in ssDNA nearly 40-fold. APE1 has a strong stimulatory effect on hSMUG1 against dsU, apparently because of enhanced dissociation of hSMUG1 from AP sites in dsDNA. hSMUG1 also has a broader substrate specificity than hUNG2, including 5-hydroxymethyluracil and 3,N(4)-ethenocytosine. hUNG2 is excluded from, whereas hSMUG1 accumulates in, nucleoli in living cells. In contrast, only hUNG2 accumulates in replication foci in the S-phase. hUNG2 in nuclear extracts initiates base excision repair of plasmids containing either U:A and U:G in vitro. Moreover, an additional but delayed repair of the U:G plasmid is observed that is not inhibited by neutralizing antibodies against hUNG2 or hSMUG1. We propose a model in which hUNG2 is responsible for both prereplicative removal of deaminated cytosine and postreplicative removal of misincorporated uracil at the replication fork. We also provide evidence that hUNG2 is the major enzyme for removal of deaminated cytosine outside of replication foci, with hSMUG1 acting as a broad specificity backup.

AB - hUNG2 and hSMUG1 are the only known glycosylases that may remove uracil from both double- and single-stranded DNA in nuclear chromatin, but their relative contribution to base excision repair remains elusive. The present study demonstrates that both enzymes are strongly stimulated by physiological concentrations of Mg2+, at which the activity of hUNG2 is 2-3 orders of magnitude higher than of hSMUG1. Moreover, Mg2+ increases the preference of hUNG2 toward uracil in ssDNA nearly 40-fold. APE1 has a strong stimulatory effect on hSMUG1 against dsU, apparently because of enhanced dissociation of hSMUG1 from AP sites in dsDNA. hSMUG1 also has a broader substrate specificity than hUNG2, including 5-hydroxymethyluracil and 3,N(4)-ethenocytosine. hUNG2 is excluded from, whereas hSMUG1 accumulates in, nucleoli in living cells. In contrast, only hUNG2 accumulates in replication foci in the S-phase. hUNG2 in nuclear extracts initiates base excision repair of plasmids containing either U:A and U:G in vitro. Moreover, an additional but delayed repair of the U:G plasmid is observed that is not inhibited by neutralizing antibodies against hUNG2 or hSMUG1. We propose a model in which hUNG2 is responsible for both prereplicative removal of deaminated cytosine and postreplicative removal of misincorporated uracil at the replication fork. We also provide evidence that hUNG2 is the major enzyme for removal of deaminated cytosine outside of replication foci, with hSMUG1 acting as a broad specificity backup.

KW - Animals

KW - Binding Sites

KW - Cattle

KW - Cell Cycle

KW - Cell Nucleus/metabolism

KW - Chromatin/metabolism

KW - Cloning, Molecular

KW - DNA Glycosylases

KW - DNA Repair

KW - DNA, Single-Stranded/chemistry

KW - Dose-Response Relationship, Drug

KW - HeLa Cells

KW - Humans

KW - Immunoglobulin G/metabolism

KW - Kinetics

KW - Magnesium Chloride/pharmacology

KW - Microscopy, Fluorescence

KW - Models, Biological

KW - N-Glycosyl Hydrolases/chemistry

KW - Polymerase Chain Reaction

KW - Promoter Regions, Genetic

KW - Protein Binding

KW - Recombinant Proteins/metabolism

KW - Salts/pharmacology

KW - Substrate Specificity

KW - Tumor Cells, Cultured

KW - Uracil/chemistry

KW - Uracil-DNA Glycosidase

U2 - 10.1074/jbc.M207107200

DO - 10.1074/jbc.M207107200

M3 - Journal article

C2 - 12161446

VL - 277

SP - 39926

EP - 39936

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 42

ER -

ID: 213363043