title: NFBD1/KIAA0170 is a chromatin-associated protein involved in DNA damage signaling pathways.
abstract: NFBD1/KIAA0170 is a nuclear factor with an N-terminal FHA (forkhead-associated) domain and a tandem repeat of BRCT (breast cancer susceptibility gene-1 C terminus) domains, both of which are present in a number of proteins involved in DNA repair and/or DNA damage signaling pathways. We have investigated the association of NFBD1 with DNA damage responses. We found that the NFBD1 transcript is abundant in the testis relative to other tissues. NFBD1 is a chromatin-associated protein and is modified in G(2)/M phase or after DNA damage. NFBD1 phosphorylation in response to ionizing radiation (IR) was ATM-dependent. NFBD1 exhibited diffuse nuclear staining in the majority of untreated cells analyzed by indirect immunofluorescence and formed discrete nuclear foci after exposure to IR, UV radiation, and hydroxyurea treatment. IR induced NFBD1 foci within 1 min. The foci colocalized with gamma-H2AX foci, which have been previously shown to localize at sites of DNA double-strand breaks. IR-induced NFBD1 foci also colocalized with 53BP1 and MRE11/RAD50 foci. Taken together, these results suggest that NFBD1 is a mediator of DNA damage-dependent signaling.
authors.affiliation: Department of Pathology, School of Medicine, Yale University, New Haven, Connecticut 06510, USA.
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Xu
authors.forename: David F
authors.initials: DF
authors.lastname: Stern
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002843:Chromatin / Q000378:metabolism*; D004249:DNA Damage; D017931:DNA Primers; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D016195:G2 Phase; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D002843:Chromatin; D017931:DNA Primers; D004268:DNA-Binding Proteins; C413163:MDC1 protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators