Developmental Arrest of Caenorhabditis elegans BRAP-2 Mutant Exposed to Oxidative Stress Is Dependent on BRC-1

作者：Koon Janet C; Kubiseski Terrance J^*

来源：Journal of Biological Chemistry, 2010, 285(18): 13437-13443.

DOI：10.1074/jbc.M110.107011

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.

• 出版日期2010-4-30