The NEF4 complex regulates Rad4 levels and utilizes Snf2/Swi2-related ATPase activity for nucleotide excision repair

Molecular and Cellular Biology
Kerrington L RamseyDavid T Auble

Abstract

Nucleotide excision repair factor 4 (NEF4) is required for repair of nontranscribed DNA in Saccharomyces cerevisiae. Rad7 and the Snf2/Swi2-related ATPase Rad16 are NEF4 subunits. We report previously unrecognized similarity between Rad7 and F-box proteins. Rad16 contains a RING domain embedded within its ATPase domain, and the presence of these motifs in NEF4 suggested that NEF4 functions as both an ATPase and an E3 ubiquitin ligase. Mutational analysis provides strong support for this model. The Rad16 ATPase is important for NEF4 function in vivo, and genetic analysis uncovered new interactions between NEF4 and Rad23, a repair factor that links repair to proteasome function. Elc1 is the yeast homologue of a mammalian E3 subunit, and it is a novel component of NEF4. Moreover, the E2s Ubc9 and Ubc13 were linked to the NEF4 repair pathway by genetic criteria. Mutations in NEF4 or Ubc13 result in elevated levels of the DNA damage recognition protein Rad4 and an increase in ubiquitylated species of Rad23. As Rad23 also controls Rad4 levels, these results suggest a complex system for globally regulating repair activity in vivo by controlling turnover of Rad4.

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Citations

Jan 22, 2009·Cell Biochemistry and Biophysics·Nancy TranWilliam K Kaufmann
Nov 19, 2009·Proceedings of the National Academy of Sciences of the United States of America·Michelle HarremanJesper Q Svejstrup
May 14, 2008·The Journal of Biological Chemistry·Milica MomcilovicMarian Carlson
Dec 17, 2004·Nucleic Acids Research·Tatiana G OrtolanKiran Madura
Jul 21, 2005·Nucleic Acids Research·Qi-En WangAltaf A Wani
Jun 2, 2006·Nucleic Acids Research·Andrew FlausTom Owen-Hughes
Feb 24, 2009·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Ling ZhangFeng Gong
Feb 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Maria G KapetanakiArthur S Levine
Feb 13, 2007·Mutation Research·Mary Ann OsleyJac A Nickoloff
Aug 15, 2009·The EMBO Journal·Staton L WadeDavid T Auble
Nov 14, 2006·FEMS Microbiology Reviews·Peter LehoczkýMiroslav Chovanec
Jan 8, 2011·Molecular Cell·Rati VermaRaymond J Deshaies
Sep 25, 2014·Frontiers in Genetics·Nealia C M HouseCatherine H Freudenreich
Oct 12, 2011·Acta Biochimica Et Biophysica Sinica·Jia LiWei Xiao
Aug 8, 2017·International Journal of Molecular Sciences·Jens Stadler, Holger Richly
Apr 3, 2013·Genetics·Serge Boiteux, Sue Jinks-Robertson

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