Open AccessAurora A kinase is required for activation of the Fanconi anemia/ BRCA pathway upon DNA damage
Author(s) -
Chun Min Jeong,
Hwang Soo Kyung,
Kim Hyoun Geun,
Goh SungHo,
Kim Sunshin,
Lee ChangHun
Publication year - 2016
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12087
Subject(s) - fanconi anemia , dna , chemistry , dna repair , biochemistry
Previous studies have linked the DNA damage response to mitotic progression machinery. Mitotic kinases, such as Aurora A kinase and Polo‐like kinase, are involved in the phosphorylation of cell cycle regulators in response to DNA damage. Here, we investigated the potential involvement of Aurora A kinase in the activation of the Fanconi anemia ( FA )/ BRCA pathway, which participates in cellular response to DNA interstrand cross‐link lesions ( ICL ). Initially, we detected interactions between Aurora A kinase and FANCA protein, one of the components of the FA nuclear core complex. Silencing of Aurora A kinase led to inhibition of monoubiquitination of FANCD 2 and formation of nuclear foci, the final consequences of FA / BRCA pathway activation upon ICL induction. An in vitro kinase assay revealed that Aurora A kinase phosphorylates S165 of FANCA . Moreover, this phosphorylation event was induced by the treatment with mitomycin C ( MMC ), an ICL ‐inducing agent. In cells overexpressing S165A mutant FANCA , monoubiquitination of FANCD 2 and nuclear foci formation was impaired and cellular sensitivity to MMC was enhanced. These results suggest that S165 phosphorylation by Aurora A kinase is required for proper activation of the FA / BRCA pathway in response to DNA damage.