Poster Discussion on Genomic Damage and Repair

Tuesday, October 18, 2005 3:30 PM-5:00 PM Room No. 601
Chair(s): Turner, Joan; Winters, Tom

(PD023) Implication of interaction between catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and BRCA1.

Lee, Kyung-Jong *,1, Yajima, Hirohiko1, Qin, Jun2, Chen, Benjamin1, Chen, David1, 1 Division of Molecular Radiation Biology, Department of Radiation Oncology, Dallas, TX, USA2 Department of Molecular and Cellular Biology, Houston, TX, USA

ABSTRACT- Non-homologous End-Joining (NHEJ) and Homologous Recombination (HR), the two major DNA double-strand break (DSB) repair pathways in mammalian cells are working coordinately to obtain the maximum efficiency of DSB repair throughout different stages of cell cycle. DNA-PKcs plays a key role in NHEJ, and BRCA1, composites of BASC, is involved in HR. However, it is not clear yet how these two pathways are regulated during the different stages of cell cycle and it has also been suggested that these two pathways may be mutually regulated. We have previously reported that ionizing radiation (IR)-induced DNA-PKcs autophosphorylation at serine 2056 is robust in G1 phase but is attenuated in S-phase. In contrast, DNA-PKcs is autophosphorylated upon DSBs caused by DNA replication-stresses, suggesting that DNA-PKcs may be preferentially activated in the S-phase (Chen et al., JBC 280:14709-15). It is known that BRCA1 is predominantly expressed in S phase, implying that the coordinative function of these two proteins may play a role in DSB repair during S phase. In this study, we show in vivo evidence of interaction between DNA-PKcs and BRCA1. In addition, immunostaining study shows that the phosphorylated DNA-PKcs and BRCA1 are co-localized upon replication stress. Taken together, we hypothesize that BRCA1 may regulate the activity of DNA-PKcs during cell cycle. (This work was supported by NIH)

Key words: dna-pkcs, brca1, nhej, hr

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2005 RRS