Details

Autor(en) / Beteiligte

• Lao, Jessica P
• Ulrich, Katie M
• Johnson, Jeffrey R
• Newton, Billy W
• Vashisht, Ajay A
• Wohlschlegel, James A
• Krogan, Nevan J
• Toczyski, David P

Titel

The Yeast DNA Damage Checkpoint Kinase Rad53 Targets the Exoribonuclease, Xrn1

Ist Teil von

• G3 : genes - genomes - genetics, 2018-12, Vol.8 (12), p.3931-3944

Ort / Verlag

England: Genetics Society of America

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• The highly conserved DNA damage response (DDR) pathway monitors the genomic integrity of the cell and protects against genotoxic stresses. The apical kinases, Mec1 and Tel1 (ATR and ATM in human, respectively), initiate the DNA damage signaling cascade through the effector kinases, Rad53 and Chk1, to regulate a variety of cellular processes including cell cycle progression, DNA damage repair, chromatin remodeling, and transcription. The DDR also regulates other cellular pathways, but direct substrates and mechanisms are still lacking. Using a mass spectrometry-based phosphoproteomic screen in , we identified novel targets of Rad53, many of which are proteins that are involved in RNA metabolism. Of the 33 novel substrates identified, we verified that 12 are directly phosphorylated by Rad53 : Xrn1, Gcd11, Rps7b, Ded1, Cho2, Pus1, Hst1, Srv2, Set3, Snu23, Alb1, and Scp160. We further characterized Xrn1, a highly conserved 5' exoribonuclease that functions in RNA degradation and the most enriched in our phosphoproteomics screen. Phosphorylation of Xrn1 by Rad53 does not appear to affect Xrn1's intrinsic nuclease activity , but may affect its activity or specificity .