Using western blotting it was shown that GA inhibited the protein expressions of MDC1, O(6)-methylguanine-DNA methyltransferase (MGMT), p-H2A.X, p53, DNA-dependent serine/threonine protein kinase (DNA-PK) and 14-3-3 proteins sigma (14-3-3σ) but increased p-p53, phosphate-ataxia-telangiectasia (p-H2A.X) and ataxia telangiectasia mutated and Rad3-related (p-ATR), phosphate-ataxia telangiectasia mutated (p-ATM) and breast cancer susceptibility protein 1 (BRCA1) in a 24-h treatment.
This network consists of many proteins that maintain genome integrity, including ataxia telangiectasia and Rad3 related protein (ATR), Bloom syndrome protein (BLM), and BRCA1.
However, caffeine enhanced the induction of micronuclei by gamma irradiation only in normal and heterozygous AT cells but not in BRCA1 cells, thus indicating a difference in the pathways leading to mutagen sensitivity in cells with a BRCA1 or an AT mutation.
Our understanding of the molecular basis of familial breast cancer has advanced significantly through investigation of the tumor suppressor gene BRCA1, as has our knowledge of the role of the ATM gene and predisposition to breast cancer in ataxia-telangiectasia carriers.
Results from this study indicate that the checkpoint protein kinase ATM (mutated in ataxia telangiectasia) was required for phosphorylation of Brca1 in response to ionizing radiation.