title: The BRCA2 is a histone acetyltransferase.
abstract: Patients carrying mutations in BRCA1 or BRCA2 tumor suppressor genes have shown to have high risk in developing breast and ovarian cancers. Two potential functions of BRCA2 were proposed which includes role in the regulation of transcription and also in DNA repair. Forty-five-amino acid region encoded by exon 3 of BRCA2 was shown to have transcriptional activation function. Recent studies of the several enzymes involved in acetylation and deacetylation of histone residues have revealed a possible relationship between gene transcriptional activation and histone acetylation. Since BRCA2 appear to function as a transcriptional factor, we have tested for Histone acetyl transferase (HAT) activity of BRCA2. Here, we present evidence that BRCA2 has intrinsic HAT activity, which maps to the amino-terminal region of BRCA2. Our results demonstrate that BRCA2 proteins acetylate primarily H3 and H4 of free histones. These observations suggest that HAT activity of BRCA2 may play an important role in the regulation of transcription and tumor suppressor function.
authors.affiliation: Department of Human Genetics, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19102, USA.
authors.forename: H
authors.initials: H
authors.lastname: Siddique
authors.forename: J P
authors.initials: JP
authors.lastname: Zou
authors.forename: V N
authors.initials: VN
authors.lastname: Rao
authors.forename: E S
authors.initials: ES
authors.lastname: Reddy
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000502:physiology*; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D024682:BRCA2 Protein; D005819:Genetic Markers; D006657:Histones; D009363:Neoplasm Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000123:Acetyltransferases; D051548:Histone Acetyltransferases