|
Beschreibung
|
A eukaryotic cell must rapidly and reversibly alter its patterns of gene expression inresponse to changes in its environment to function effectively. One of the most lethallesions that can occur in a cell is a DNA doublestrand break which disrupts the integrityof the DNA molecule. DNA double-strand breaks (dsbs) are introduced by x-rays andoxidative metabolism and theirrepair is essential to cell survival. This is achieved through modulation of the activity ofsequence-specific, DNA-binding transcription factors that is often mediated byphosphorylation. This phosphorylation requires the presence of DNA and is catalyzed bythe DNAdependent protein kinase (DNA-PK).1,2 DNA-PK, also known astemplate-associated protein kinase, is aserine/threonine kinase that is absolutely dependent for activity on binding todouble-stranded DNA containing broken ends, nicks and single-stranded gaps. DNA-PKphosphorylates many protein substrates in vitro including the 90 kDa heat-shock protein(hsp90), Sp1, SV40 T antigen, the tumor suppressor protein p53, serum response factor(SRF), fos, jun, and the C-terminal domain (CTD) of RNA polymerase II.2 In thiscapacity, itplays a key role in initiation of transcription. DNA-PK has been purified andcharacterized from many human cells and tissues and consists of at least two proteincomponents, a large polypeptide of approximately 350 kDa (p350) and the Kuautoantigen. The p350component binds adenosine triphosphate (ATP) analogs and contains the kinasedomain of DNA-PK. The Ku protein is a heterodimer composed of two subunits, 70 kDaand 86 kDa (80 in some publications), that was originally detected as an autoantigenreacting with antibodies from patients with rheumatic disorders.3 The biochemicalproperties of both Ku and DNA-PK suggest that they have a role in DNA damagedetection or in repair or in both processes. The localization of thisprotein complex to the DNase-sensitive regions in the chromatin was the first indicationthat the Ku protein may be involved in active DNA processes such as transcription,replication, or repair. For instance, it was reported that the Ku protein is involved inspecific binding to the promoter region of human transferrin receptor gene and to theproximal and distal promoter elements of the U1 snRNA gene. The in vitro transcriptionof U1 snRNA gene depends to a large extent on the presence of the Ku protein.4 Kuinteracts with the terminals ofdouble-stranded DNA through the 70 kDa subunit and by this means provides the DNAtargeting required by DNAPK. Ku p86 has been identified as the XRCC5 (human DNArepair gene product), thus it is involved in DNA repair and in V(D)J recombination. Kucan complement both the radiosensitivity and the V(D)J deficientphenotypes of radiosensitive (XRS) cell lines.5,6 Monoclonal antibody reactingspecifically with the p86 subunit of the Ku protein may be used to study of the processesinvolved in the genetic expression. Alternate Names: anti-ATP dependent DNA helicase II 80 kDa subunit antibody, anti-ATP dependent DNAhelicase II 86 Kd subunit antibody, anti-CTC box binding factor 85 kDa antibody,anti-CTC85 antibody, anti-CTCBF antibody, anti-DNA repair protein XRCC5 antibody,anti-KARP1 antibody, anti-Ku86 autoantigen related protein 1 antibody, anti-NFIVantibody, anti-Nuclear factor IV antibody, anti-Thyroid lupus autoantigen antibody,anti-TLAA antibody, anti-Xray repair complementing defective repair in Chinese hamster
|
Alternativen 
