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PMID:19111656

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Citation

Kim, SH and Michael, WM (2008) Regulated proteolysis of DNA polymerase eta during the DNA-damage response in C. elegans. Mol. Cell 32:757-66

Abstract

Both the POLH-1 (pol eta) translesion synthesis (TLS) DNA polymerase and the GEI-17 SUMO E3 ligase are essential for the efficient replication of damaged chromosomes in Caenorhabditis elegans embryos. Here we study how POLH-1 is regulated during a DNA-damage response in these embryos. We report that DNA damage triggers the degradation of POLH-1 and that degradation is mediated by the Cul4-Ddb1-Cdt2 (CRL4-Cdt2) pathway that has previously been shown to degrade the replication factor Cdt1 during S phase. We also show that GEI-17 protects POLH-1 from CRL4-Cdt2-mediated destruction until after it has performed its function in TLS, and this is likely via SUMOylation of POLH-1. These studies reveal that POLH-1 undergoes DNA-damage-induced proteolysis and that GEI-17 regulates the timing of this proteolysis. Implications for how this system may control the removal of POLH-1 from replication forks after TLS are discussed.

Links

PubMed PMC2646262 Online version:10.1016/j.molcel.2008.11.016

Keywords

Animals; Caenorhabditis elegans/cytology; Caenorhabditis elegans/drug effects; Caenorhabditis elegans/embryology; Caenorhabditis elegans/enzymology; Caenorhabditis elegans Proteins/metabolism; DNA Damage; DNA-Directed DNA Polymerase/metabolism; Embryo, Nonmammalian/cytology; Embryo, Nonmammalian/drug effects; Embryo, Nonmammalian/enzymology; Genome; Methyl Methanesulfonate/pharmacology; Models, Biological; Protein Processing, Post-Translational/drug effects; Small Ubiquitin-Related Modifier Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:G5EFY1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O02115

F

Seeded From UniProt

complete

CAEEL:G5EFY1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:G5EFY1

involved_in

GO:0042276: error-prone translesion synthesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:PCNA

enables

GO:0070182: DNA polymerase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:G5EFY1

F

Seeded From UniProt

complete

CAEEL:DDB1

involved_in

GO:0043161: proteasome-mediated ubiquitin-dependent protein catabolic process

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00001574

P

Seeded From UniProt

complete

CAEEL:Q22059

involved_in

GO:0043161: proteasome-mediated ubiquitin-dependent protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:Q22059

involved_in

GO:0043161: proteasome-mediated ubiquitin-dependent protein catabolic process

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00001574

P

Seeded From UniProt

complete

CAEEL:GEI17

involved_in

GO:0016925: protein sumoylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:GEI17

involved_in

GO:0016925: protein sumoylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • happens_during:(GO:0006974)
  • happens_during:(WBls:0000003)

Seeded From UniProt

complete

CAEEL:GEI17

located_in

GO:0000785: chromatin

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:GEI17

enables

GO:0061665: SUMO ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(WB:WBGene00018721)

Seeded From UniProt

complete

CAEEL:GEI17

involved_in

GO:1903363: negative regulation of cellular protein catabolic process

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(WB:WBGene00018721)
  • happens_during:(GO:0006974)
  • happens_during:(WBls:0000003)

Seeded From UniProt

complete

CAEEL:GEI17

involved_in

GO:1903363: negative regulation of cellular protein catabolic process

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00000839

P

  • has_input:(WB:WBGene00018721)
  • happens_during:(GO:0006974)
  • happens_during:(WBls:0000003)

Seeded From UniProt

complete

CAEEL:GEI17

involved_in

GO:1903363: negative regulation of cellular protein catabolic process

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00010890

P

  • has_input:(WB:WBGene00018721)
  • happens_during:(GO:0006974)
  • happens_during:(WBls:0000003)

Seeded From UniProt

complete

CAEEL:GEI17

involved_in

GO:1903363: negative regulation of cellular protein catabolic process

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00003955

P

  • has_input:(WB:WBGene00018721)
  • happens_during:(GO:0006974)
  • happens_during:(WBls:0000003)

Seeded From UniProt

complete

CAEEL:GEI17

involved_in

GO:1903363: negative regulation of cellular protein catabolic process

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00011318

P

  • has_input:(WB:WBGene00018721)
  • happens_during:(GO:0006974)
  • happens_during:(WBls:0000003)

Seeded From UniProt

complete

CAEEL:UBC9

involved_in

GO:0016925: protein sumoylation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

CAEEL:UBC9

enables

GO:0061656: SUMO conjugating enzyme activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(WB:WBGene00018721)

Seeded From UniProt

complete

CAEEL:CUL4

involved_in

GO:0043161: proteasome-mediated ubiquitin-dependent protein catabolic process

ECO:0000316: genetic interaction evidence used in manual assertion

WB:WBGene00001574

P

Seeded From UniProt

complete


See also

References

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