Department of Cancer Biology; Department of Biochemistry and Molecular Pharmacology
Acetylation; Basic-Leucine Zipper Transcription Factors; DNA; DNA Damage; Fanconi Anemia Complementation Group Proteins; Lysine
Biochemistry, Biophysics, and Structural Biology | Cancer Biology | Genetics and Genomics | Life Sciences | Medicine and Health Sciences
BRCA1 promotes DNA repair through interactions with multiple proteins, including CtIP and FANCJ (also known as BRIP1/BACH1). While CtIP facilitates DNA end resection when de-acetylated, the function of FANCJ in repair processing is less well defined. Here, we report that FANCJ is also acetylated. Preventing FANCJ acetylation at lysine 1249 does not interfere with the ability of cells to survive DNA interstrand crosslinks (ICLs). However, resistance is achieved with reduced reliance on recombination. Mechanistically, FANCJ acetylation facilitates DNA end processing required for repair and checkpoint signaling. This conclusion was based on the finding that FANCJ and its acetylation were required for robust RPA foci formation, RPA phosphorylation, and Rad51 foci formation in response to camptothecin (CPT). Furthermore, both preventing and mimicking FANCJ acetylation at lysine 1249 disrupts FANCJ function in checkpoint maintenance. Thus, we propose that the dynamic regulation of FANCJ acetylation is critical for robust DNA damage response, recombination-based processing, and ultimately checkpoint maintenance.
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Copyright: © 2012 Cantor et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
Xie J, Peng M, Guillemette S, Quan S, Maniatis S, et al. (2012) FANCJ/BACH1 Acetylation at Lysine 1249 Regulates the DNA Damage Response. PLoS Genet 8(7): e1002786. doi:10.1371/journal.pgen.1002786. Link to article on publisher's site
Xie, Jenny X.; Peng, Min; Guillemette, Shawna; Quan, Steven; Maniatis, Stephanie; Wu, Yuliang; Venkatesh, Aditya; Shaffer, Scott A.; Brosh, Robert M. Jr.; and Cantor, Sharon B., "FANCJ/BACH1 Acetylation at Lysine 1249 Regulates the DNA Damage Response" (2012). Open Access Articles. 2332.