Defects in DNA ligase I trigger PCNA ubiquitylation at Lys 107 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-01

AUTHORS

Sapna Das-Bradoo, Hai Dang Nguyen, Jamie L. Wood, Robin M. Ricke, Justin C. Haworth, Anja-Katrin Bielinsky

ABSTRACT

In all eukaryotes, the ligation of newly synthesized DNA, also known as Okazaki fragments, is catalysed by DNA ligase I (ref. 1). An individual with a DNA ligase I deficiency exhibits growth retardation, sunlight sensitivity and severe immunosuppression, probably due to accumulation of DNA damage. Surprisingly, not much is known about the DNA damage response (DDR) in DNA ligase I-deficient cells. As DNA replication and DDR pathways are highly conserved in eukaryotes, we used Saccharomyces cerevisiae as a model system to address this issue. We uncovered a new pathway, which facilitates ubiquitylation at Lys 107 of proliferating cell nuclear antigen (PCNA). Unlike ubiquitylation at Lys 164 of PCNA in response to UV irradiation, which triggers translesion synthesis, modification of Lys 107 is not dependent on the ubiquitin conjugating enzyme (E2) Rad6 (ref. 4) nor the ubiquitin ligase (E3) Rad18 (ref. 5), but requires the E2 variant Mms2 (ref. 6) in conjunction with Ubc4 (ref. 7) and the E3 Rad5 (Refs 8, 9). Surprisingly, DNA ligase I-deficient S. cerevisiae cdc9-1 cells that carry a PCNAK107R mutation are inviable, because they cannot activate a robust DDR. Furthermore, we show that ubiquitylation of PCNA in response to DNA ligase I deficiency is conserved in humans, yet the lysine residue that is modified remains to be determined. We propose that PCNA ubiquitylation provides a 'DNA damage code' that allows cells to categorize different types of defects that arise during DNA replication. More... »

PAGES

74-79

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncb2007

DOI

http://dx.doi.org/10.1038/ncb2007

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1025475538

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20010813


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Download the RDF metadata as:  json-ld nt turtle xml License info

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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/ncb2007'


 

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