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Rtt101 and Mms1 in budding yeast form a CUL4(DDB1)-like ubiquitin ligase that promotes replication through damaged DNA

Zaidi, Iram Waris; Rabut, Gwénaël; Poveda, Ana; Scheel, Hartmut; Malmström, Johan LU ; Ulrich, Helle; Hofmann, Kay; Pasero, Philippe; Peter, Matthias and Luke, Brian (2008) In EMBO Reports 9(10). p.40-1034
Abstract

In budding yeast the cullin Rtt101 promotes replication fork progression through natural pause sites and areas of DNA damage, but its relevant subunits and molecular mechanism remain poorly understood. Here, we show that in budding yeast Mms1 and Mms22 are functional subunits of an Rtt101-based ubiquitin ligase that associates with the conjugating-enzyme Cdc34. Replication forks in mms1Delta, mms22Delta and rtt101Delta cells are sensitive to collisions with drug-induced DNA lesions, but not to transient pausing induced by nucleotide depletion. Interaction studies and sequence analysis have shown that Mms1 resembles human DDB1, suggesting that Rtt101(Mms1) is the budding yeast counterpart of the mammalian CUL4(DDB1) ubiquitin ligase... (More)

In budding yeast the cullin Rtt101 promotes replication fork progression through natural pause sites and areas of DNA damage, but its relevant subunits and molecular mechanism remain poorly understood. Here, we show that in budding yeast Mms1 and Mms22 are functional subunits of an Rtt101-based ubiquitin ligase that associates with the conjugating-enzyme Cdc34. Replication forks in mms1Delta, mms22Delta and rtt101Delta cells are sensitive to collisions with drug-induced DNA lesions, but not to transient pausing induced by nucleotide depletion. Interaction studies and sequence analysis have shown that Mms1 resembles human DDB1, suggesting that Rtt101(Mms1) is the budding yeast counterpart of the mammalian CUL4(DDB1) ubiquitin ligase family. Rtt101 interacts in an Mms1-dependent manner with the putative substrate-specific adaptors Mms22 and Crt10, the latter being a regulator of expression of ribonucleotide reductase. Taken together, our data suggest that the Rtt101(Mms1) ubiquitin ligase complex might be required to reorganize replication forks that encounter DNA lesions.

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publication status
published
keywords
Anaphase-Promoting Complex-Cyclosome, Cullin Proteins, DNA Damage, DNA Replication, DNA-Binding Proteins, Humans, Protein Subunits, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Ubiquitin-Conjugating Enzymes, Ubiquitin-Protein Ligase Complexes, Ubiquitin-Protein Ligases, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
in
EMBO Reports
volume
9
issue
10
pages
7 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:53249151607
ISSN
1469-221X
DOI
10.1038/embor.2008.155
language
English
LU publication?
no
id
c2594638-9c39-4234-a612-d12b66736d69
date added to LUP
2017-09-04 17:21:25
date last changed
2017-09-10 05:23:42
@article{c2594638-9c39-4234-a612-d12b66736d69,
  abstract     = {<p>In budding yeast the cullin Rtt101 promotes replication fork progression through natural pause sites and areas of DNA damage, but its relevant subunits and molecular mechanism remain poorly understood. Here, we show that in budding yeast Mms1 and Mms22 are functional subunits of an Rtt101-based ubiquitin ligase that associates with the conjugating-enzyme Cdc34. Replication forks in mms1Delta, mms22Delta and rtt101Delta cells are sensitive to collisions with drug-induced DNA lesions, but not to transient pausing induced by nucleotide depletion. Interaction studies and sequence analysis have shown that Mms1 resembles human DDB1, suggesting that Rtt101(Mms1) is the budding yeast counterpart of the mammalian CUL4(DDB1) ubiquitin ligase family. Rtt101 interacts in an Mms1-dependent manner with the putative substrate-specific adaptors Mms22 and Crt10, the latter being a regulator of expression of ribonucleotide reductase. Taken together, our data suggest that the Rtt101(Mms1) ubiquitin ligase complex might be required to reorganize replication forks that encounter DNA lesions.</p>},
  author       = {Zaidi, Iram Waris and Rabut, Gwénaël and Poveda, Ana and Scheel, Hartmut and Malmström, Johan and Ulrich, Helle and Hofmann, Kay and Pasero, Philippe and Peter, Matthias and Luke, Brian},
  issn         = {1469-221X},
  keyword      = {Anaphase-Promoting Complex-Cyclosome,Cullin Proteins,DNA Damage,DNA Replication,DNA-Binding Proteins,Humans,Protein Subunits,Saccharomyces cerevisiae,Saccharomyces cerevisiae Proteins,Ubiquitin-Conjugating Enzymes,Ubiquitin-Protein Ligase Complexes,Ubiquitin-Protein Ligases,Comparative Study,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  number       = {10},
  pages        = {40--1034},
  publisher    = {Nature Publishing Group},
  series       = {EMBO Reports},
  title        = {Rtt101 and Mms1 in budding yeast form a CUL4(DDB1)-like ubiquitin ligase that promotes replication through damaged DNA},
  url          = {http://dx.doi.org/10.1038/embor.2008.155},
  volume       = {9},
  year         = {2008},
}