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Rtt101 and Mms1 in budding yeast form a CUL4 DDB1 ‐like ubiquitin ligase that promotes replication through damaged DNA
Author(s) -
Zaidi Iram Waris,
Rabut Gwénaël,
Poveda Ana,
Scheel Hartmut,
Malmström Johan,
Ulrich Helle,
Hofmann Kay,
Pasero Philippe,
Peter Matthias,
Luke Brian
Publication year - 2008
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2008.155
Subject(s) - ddb1 , ubiquitin ligase , biology , dna ligase , cell division control protein 4 , dna replication , ubiquitin , eukaryotic dna replication , replication factor c , control of chromosome duplication , microbiology and biotechnology , dna repair , ribonucleotide reductase , origin recognition complex , dna , genetics , protein subunit , gene
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 mms1 Δ, mms22 Δ and rtt101 Δ 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.