RGD Reference Report - Human SAD1 kinase is involved in UV-induced DNA damage checkpoint function. - Rat Genome Database

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Human SAD1 kinase is involved in UV-induced DNA damage checkpoint function.

Authors: Lu, R  Niida, H  Nakanishi, M 
Citation: Lu R, etal., J Biol Chem. 2004 Jul 23;279(30):31164-70. Epub 2004 May 18.
RGD ID: 8554801
Pubmed: PMID:15150265   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M404728200   (Journal Full-text)

Checkpoint activation by DNA damage during G(2) prevents activation of cyclin B/Cdc2 complexes, and as a consequence, mitotic entry is blocked. Although initiation and maintenance of G(2) arrest are known to be regulated by at least two distinct signaling pathways, including those of p38MAPK and ataxia-telangiectasia-mutated (ATM)- and Rad3-related (ATR)-Chk1 in higher eukaryotes, the actual number of signaling pathways involved in this regulation is still elusive. In the present study, we identified human SAD1 (hsSAD1) by searching a sequence data base. The predicted hsSAD1 protein comprises 778 amino acids and shares significant homology with the fission yeast Cdr2, a mitosis-regulatory kinase, and Caenorhabditis elegans SAD1, a neuronal cell polarity regulator. HsSAD1 transcript was expressed ubiquitously with the highest levels of expression in brain and testis. HsSAD1 specifically phosphorylated Wee1A, Cdc25-C, and -B on Ser-642, Ser-216, and Ser-361 in vitro, respectively. Overexpression of hsSAD1 resulted in an increased phosphorylation of Cdc25C on Ser-216 in vivo. DNA damage induced by UV or methyl methane sulfonate but not by IR enhanced endogenous hsSAD1 kinase activity in a caffeine-sensitive manner and caused translocation of its protein from cytoplasm to nucleus. Overexpression of wild-type hsSAD1 induced G(2)/M arrest in HeLa S2 cells. Furthermore, UV-induced G(2)/M arrest was partially abrogated by the reduced expression of hsSAD1 using small interfering RNA. These results suggest that hsSAD1 acts as checkpoint kinase upon DNA damage induced by UV or methyl methane sulfonate. The identification of this new kinase suggests the existence of an alternative checkpoint pathway other than those of ATR-Chk1 and p38MAPK.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Brsk2Ratcytoplasm located_inISSUniProtKB:Q8TDC3PMID:15150265UniProt 
Brsk2Ratnucleus located_inISSUniProtKB:Q8TDC3PMID:15150265UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Brsk2Ratprotein serine/threonine kinase activity enablesISSUniProtKB:Q8TDC3PMID:15150265UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Brsk2  (BR serine/threonine kinase 2)


Additional Information