p300-mediated acetylation of the Rothmund-Thomson-syndrome gene product RECQL4 regulates its subcellular localization

0333651 - ÚMG 2010 RIV GB eng J - Journal Article
Dietschy, T. - Shevelev, Igor - Pena-Diaz, J. - Hühn, D. - Kuenzle, S. - Mak, R. - Miah, M.F. - Hess, D. - Fey, M. - Hottiger, M.O. - Janščák, Pavel - Stagljar, I.
p300-mediated acetylation of the Rothmund-Thomson-syndrome gene product RECQL4 regulates its subcellular localization.
Journal of Cell Science. Roč. 122, Pt 8 (2009), s. 1258-1267. ISSN 0021-9533. E-ISSN 1477-9137
Institutional research plan: CEZ:AV0Z50520514
Keywords : RECQL4 * RecQ helicases * Genome stability * p300 * Protein acetylation
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 6.144, year: 2009

RECQL4 belongs to the conserved RecQ family of DNA helicases playing important roles in the maintenance of genome stability. Although genetic alterations in RECQL4 gene are reported to be associated with three autosomal recessive disorders, the molecular role of RECQL4 is still poorly understood. We show that RECQL4 specifically interacts with histone acetyltransferase p300 (p300 HAT) in vivo and in vitro and that p300 acetylates one or more lysine residues of RECQL4. We also report that these residues lie within a short motif of 30 aa essential for the nuclear localization of RECQL4. Acetylation of RECQL4 by p300 in vivo leads to a significant shift of a proportion of RECQL4 protein from the nucleus to the cytoplasm. This is a result of RECQL4 inability to be imported into the nucleus. Our results are the first evidence of post-translational modification of RECQL4 and suggest that acetylation of RECQL4 by p300 regulates trafficking of RECQL4 between the nucleus and the cytoplasm.
Permanent Link: http://hdl.handle.net/11104/0178590