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An Interaction between DNA Ligase I and Proliferating Cell Nuclear Antigen: Implications for Okazaki Fragment Synthesis and Joining
by
Levin, David S.
, Tomkinson, Alan E.
, Yao, Nina
, O'Donnell, Michael
, Bai, Wei
in
Biochemistry
/ Biological Sciences
/ Cellular biology
/ Chromatography, Affinity
/ Cyclin-Dependent Kinase Inhibitor p21
/ Cyclins - metabolism
/ Deoxyribonucleic acid
/ DNA
/ DNA - biosynthesis
/ DNA - metabolism
/ DNA Ligase ATP
/ DNA Ligases - metabolism
/ DNA Polymerase III - metabolism
/ DNA Replication
/ Fractionation
/ Gels
/ Goods and services tax
/ HeLa Cells
/ Humans
/ Immunoblotting
/ Molecules
/ Plasmids
/ Proliferating Cell Nuclear Antigen - metabolism
/ Protein Binding
/ Protein Processing, Post-Translational
/ Proteins
/ Resins
/ Specific retention
/ Trimers
1997
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An Interaction between DNA Ligase I and Proliferating Cell Nuclear Antigen: Implications for Okazaki Fragment Synthesis and Joining
by
Levin, David S.
, Tomkinson, Alan E.
, Yao, Nina
, O'Donnell, Michael
, Bai, Wei
in
Biochemistry
/ Biological Sciences
/ Cellular biology
/ Chromatography, Affinity
/ Cyclin-Dependent Kinase Inhibitor p21
/ Cyclins - metabolism
/ Deoxyribonucleic acid
/ DNA
/ DNA - biosynthesis
/ DNA - metabolism
/ DNA Ligase ATP
/ DNA Ligases - metabolism
/ DNA Polymerase III - metabolism
/ DNA Replication
/ Fractionation
/ Gels
/ Goods and services tax
/ HeLa Cells
/ Humans
/ Immunoblotting
/ Molecules
/ Plasmids
/ Proliferating Cell Nuclear Antigen - metabolism
/ Protein Binding
/ Protein Processing, Post-Translational
/ Proteins
/ Resins
/ Specific retention
/ Trimers
1997
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An Interaction between DNA Ligase I and Proliferating Cell Nuclear Antigen: Implications for Okazaki Fragment Synthesis and Joining
by
Levin, David S.
, Tomkinson, Alan E.
, Yao, Nina
, O'Donnell, Michael
, Bai, Wei
in
Biochemistry
/ Biological Sciences
/ Cellular biology
/ Chromatography, Affinity
/ Cyclin-Dependent Kinase Inhibitor p21
/ Cyclins - metabolism
/ Deoxyribonucleic acid
/ DNA
/ DNA - biosynthesis
/ DNA - metabolism
/ DNA Ligase ATP
/ DNA Ligases - metabolism
/ DNA Polymerase III - metabolism
/ DNA Replication
/ Fractionation
/ Gels
/ Goods and services tax
/ HeLa Cells
/ Humans
/ Immunoblotting
/ Molecules
/ Plasmids
/ Proliferating Cell Nuclear Antigen - metabolism
/ Protein Binding
/ Protein Processing, Post-Translational
/ Proteins
/ Resins
/ Specific retention
/ Trimers
1997
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An Interaction between DNA Ligase I and Proliferating Cell Nuclear Antigen: Implications for Okazaki Fragment Synthesis and Joining
Journal Article
An Interaction between DNA Ligase I and Proliferating Cell Nuclear Antigen: Implications for Okazaki Fragment Synthesis and Joining
1997
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Overview
Although three human genes encoding DNA ligases have been isolated, the molecular mechanisms by which these gene products specifically participate in different DNA transactions are not well understood. In this study, fractionation of a HeLa nuclear extract by DNA ligase I affinity chromatography resulted in the specific retention of a replication protein, proliferating cell nuclear antigen (PCNA), by the affinity resin. Subsequent experiments demonstrated that DNA ligase I and PCNA interact directly via the amino-terminal 118 aa of DNA ligase I, the same region of DNA ligase I that is required for localization of this enzyme at replication foci during S phase. PCNA, which forms a sliding clamp around duplex DNA, interacts with DNA pol δ and enables this enzyme to synthesize DNA processively. An interaction between DNA ligase I and PCNA that is topologically linked to DNA was detected. However, DNA ligase I inhibited PCNA-dependent DNA synthesis by DNA pol δ . These observations suggest that a ternary complex of DNA ligase I, PCNA and DNA pol δ does not form on a gapped DNA template. Consistent with this idea, the cell cycle inhibitor p21, which also interacts with PCNA and inhibits processive DNA synthesis by DNA pol δ , disrupts the DNA ligase I-PCNA complex. Thus, we propose that after Okazaki fragment DNA synthesis is completed by a PCNA-DNA pol δ complex, DNA pol δ is released, allowing DNA ligase I to bind to PCNA at the nick between adjacent Okazaki fragments and catalyze phosphodiester bond formation.
Publisher
National Academy of Sciences of the United States of America,National Acad Sciences,National Academy of Sciences,The National Academy of Sciences of the USA
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