RRC ID 46625
Author Koon JC, Kubiseski TJ.
Title Developmental arrest of Caenorhabditis elegans BRAP-2 mutant exposed to oxidative stress is dependent on BRC-1.
Journal J Biol Chem
Abstract Oxidative damage by reactive oxygen species is believed to be a contributor to the development of cancer and the physiological deterioration associated with aging. In this report, we describe the effect of reactive oxygen species exposure to a developing Caenorhabditis elegans organism containing a deletion in the homolog of BRCA1-associated protein 2 (BRAP-2). A mutant containing a deletion of brap-2 was highly sensitive to oxidizing conditions and demonstrated early larval arrest and lethality at low concentrations of the oxidative stress-inducing drug paraquat compared with the wild-type. This developmental arrest occurred early in the L1 stage and was dependent specifically on the function of the C. elegans ortholog of BRCA-1 tumor suppressor brc-1. We also show that developmental arrest in brap-2 mutants when exposed to oxidative stress was due to enhanced expression levels of the cell cycle inhibitor cki-1, and this increase in the expression levels of cki-1 requires brc-1 in brap-2 mutant animals. Our findings demonstrate that BRAP-2 is necessary for preventing an inappropriate response to elevated levels of reactive oxygen species by countering premature activation of BRC-1 and CKI-1.
Volume 285(18)
Pages 13437-43
Published 2010-4-30
DOI 10.1074/jbc.M110.107011
PII M110.107011
PMID 20207739
PMC PMC2859503
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Carrier Proteins / genetics Carrier Proteins / metabolism* Cyclin-Dependent Kinase Inhibitor Proteins / genetics Cyclin-Dependent Kinase Inhibitor Proteins / metabolism Gene Expression Regulation, Developmental / drug effects Gene Expression Regulation, Developmental / physiology* Herbicides / pharmacology Larva / genetics Larva / metabolism Mutation* Oxidative Stress / drug effects Oxidative Stress / physiology* Paraquat / pharmacology Reactive Oxygen Species / metabolism*
IF 4.238
Times Cited 9
C.elegans tm1145