FANCJ/BACH1 acetylation at lysine 1249 regulates the DNA damage response.
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.
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Jenny
J
Xie
Min
M
Peng
Shawna
S
Guillemette
Steven
S
Quan
Stephanie
S
Maniatis
Yuliang
Y
Wu
Aditya
A
Venkatesh
Scott A
SA
Shaffer
Robert M
RM
Brosh
Sharon B
SB
Cantor
D000107:Acetylation; D019313:BRCA1 Protein / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D009154:Mutation
C102108:BACH1 protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D051856:Fanconi Anemia Complementation Group Proteins; D004247:DNA; D051548:Histone Acetyltransferases; D008239:Lysine