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. 2010 Dec;1(12):1211-4.
doi: 10.1177/1947601911404222.

Regulation of ATM/DNA-PKcs Phosphorylation by BRCA1-Associated BAAT1

Mutsuko Ouchi  1 , Toru Ouchi
Affiliations

Regulation of ATM/DNA-PKcs Phosphorylation by BRCA1-Associated BAAT1

Mutsuko Ouchi et al. Genes Cancer. 2010 Dec.

Abstract

BRCA1 has been implicated in the DNA damage pathway and regulation of genome stability, however, it does not contain intrinsic catalytic activity to repair the DNA lesions. Thus, a potential activity of BRCA1 is to assemble proteins that sense DNA damage and to transduce checkpoint signals to downstream. We have recently isolated a protein termed BAAT1, which binds to BRCA1, ATM, DNA-PKcs, and SMC1. Phosphorylation of ATM/DNA-PKcs is greatly reduced in BAAT1-knockdown cells, suggesting that sensing of DNA lesions mediated by BRCA1/BAAT1 is critical for activation of these kinases.

Keywords: ATM; BAAT1; BRCA1; DNA damage pathway; DNA-PKcs; SMC1.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the authorship and/or publication of this article.

Figures

Figure 1.
Figure 1.
Structure and interaction interface of BAAT1. The N-terminal CIDE-N domain (light green) and 2 HEAT repeats (light red) are indicated. Ser742 is also indicated. BAAT1’s binding regions for DNA-PKcs/SMC1 or ATM are demonstrated in Figure 2.
Figure 2.
Figure 2.
Schematic model of BAAT1 function in regulating ATM/DNA-PKcs phosphorylation. BAAT1 constitutively binds to BRCT domains of BRCA1 and stress kinases such as ATM/DNA-PKcs. Phosphorylation of ATM at Ser1981 and DNA-PKcs at Ser2956 occurs under conditions of DNA stress. In this model, BAAT1 potentially protects these residues from phosphatases that dephosphorylate these residues.
See this image and copyright information in PMC

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