Publication Date:
2003-10-25
Description:
The carboxyl-terminal domain (BRCT) of the Breast Cancer Gene 1 (BRCA1) protein is an evolutionarily conserved module that exists in a large number of proteins from prokaryotes to eukaryotes. Although most BRCT domain-containing proteins participate in DNA-damage checkpoint or DNA-repair pathways, or both, the function of the BRCT domain is not fully understood. We show that the BRCA1 BRCT domain directly interacts with phosphorylated BRCA1-Associated Carboxyl-terminal Helicase (BACH1). This specific interaction between BRCA1 and phosphorylated BACH1 is cell cycle regulated and is required for DNA damage-induced checkpoint control during the transition from G2 to M phase of the cell cycle. Further, we show that two other BRCT domains interact with their respective physiological partners in a phosphorylation-dependent manner. Thirteen additional BRCT domains also preferentially bind phospho-peptides rather than nonphosphorylated control peptides. These data imply that the BRCT domain is a phospho-protein binding domain involved in cell cycle control.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Xiaochun -- Chini, Claudia Christiano Silva -- He, Miao -- Mer, Georges -- Chen, Junjie -- CA89239/CA/NCI NIH HHS/ -- CA92312/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2003 Oct 24;302(5645):639-42.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Oncology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14576433" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Motifs
;
BRCA1 Protein/*chemistry/*metabolism
;
Carrier Proteins/chemistry/metabolism
;
Cell Cycle
;
*Cell Cycle Proteins
;
Cell Line
;
DNA Damage
;
DNA Repair
;
*DNA-Binding Proteins
;
E2F Transcription Factors
;
G2 Phase
;
Humans
;
Mitosis
;
Mutation
;
Nuclear Proteins
;
Peptide Library
;
Phosphoprotein Phosphatases/chemistry/metabolism
;
Phosphoproteins/chemistry/genetics/*metabolism
;
Phosphorylation
;
Phosphoserine/metabolism
;
Protein Binding
;
Protein Structure, Tertiary
;
RNA Helicases/chemistry/genetics/*metabolism
;
RNA Polymerase II/metabolism
;
RNA, Small Interfering
;
Recombinant Fusion Proteins/chemistry/metabolism
;
Transcription Factors/metabolism
;
Transfection
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink