Human DNA topoisomerase I alpha

Abstract

Disclosed is a human is a hTopI-α polypeptide and DNA (RNA) encoding such hTopI-α polypeptide. Also provided is a procedure for producing such polypeptide by recombinant techniques and antibodies and antagonists against such polypeptide. Also provided are methods of using the antibodies and antagonist inhibitors to inhibit the action of hTopI-α for therapeutic purposes such as an antitumor agent, to detect an autoimmune disease, or retroviral infections and to treat adenocarcinoma of the colon. Diagnostic methods for detecting mutations in the coding sequence and alterations in the concentration of the polypeptides in a sample derived from a host are also disclosed.

What is claimed is:  
     
         1 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide encoding the polypeptide comprising amino acid 1 to amino acid 601 as set forth in SEQ ID NO:2    (b) a polynucleotide capable of hybridizing to and which is at least 70% identical to the polynucleotide of (a); and    (c) a polynucleotide fragment of the polynucleotide of (a) or (b).    
     
     
         2 . The polynucleotide of  claim 1  wherein the polynucleotide is DNA.  
     
     
         3 . The polynucleotide of  claim 1  wherein the polynucleotide is RNA.  
     
     
         4 . The polynucleotide of  claim 1  wherein the polynucleotide is genomic DNA.  
     
     
         5 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide which encodes a mature polypeptide having the amino acid sequence expressed by the DNA contained in ATCC Deposit No. 75714;    (b) a polynucleotide which encodes a polypeptide having the amino acid sequence expressed by the DNA contained in ATCC Deposit No. 75714;    (c) a polynucleotide capable of hybridizing to and which is at least 70% identical to the polynucleotide of (a); and    (d) a polynucleotide fragment of the polynucleotide of (a), (b) or (c).    
     
     
         6 . The polynucleotide of  claim 1  comprising the sequence as set forth in SEQ ID No. 1 from nucleotide 1 to nucleotide 1917.  
     
     
         7 . A vector containing the DNA of  claim 2 .  
     
     
         8 . A host cell genetically engineered with the vector of  claim 7 .  
     
     
         9 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 8  the polypeptide encoded by said DNA.  
     
     
         10 . A process for producing cells capable of expressing a polypeptide comprising genetically engineering cells with the vector of  claim 7 .  
     
     
         11 . A polypeptide selected from the group consisting of (i) a polypeptide having~the deduced amino acid sequence of SEQ ID NO:2 and fragments, analogs and derivatives thereof; 
 and (ii) a polypeptide encoded by the cDNA of ATCC Deposit No. 75714 and fragments, analogs and derivatives of said polypeptide.    
     
     
         12 . The polypeptide of  claim 11  wherein the polypeptide comprises amino acid 1 to amino acid 601 of SEQ ID NO:2.  
     
     
         13 . A compound which inhibits the polypeptide of  claim 11 .  
     
     
         14 . A method for the treatment of a patient having need of hTopI-α comprising: administering to the patient a therapeutically effective amount of the polypeptide of  claim 11 .  
     
     
         15 . The method of  claim 14  wherein said therapeutically effective amount of the polypeptide is administered by providing to the patient DNA encoding said polypeptide and expressing said polypeptide in vivo.  
     
     
         16 . A method for the treatment of a patient having need to inhibit ahtopI-α polypeptide comprising: 
 administering to the patient a therapeutically effective amount of the compound of  claim 13 .  
 
     
     
         17 . A process for diagnosing a disease or a susceptibility to a disease related to expression of the polypeptide of  claim 11  comprising: 
 determining a mutation in a nucleic acid sequence encoding said polypeptide.  
 
     
     
         18 . A diagnostic process comprising: 
 analyzing for the presence of the polypeptide of  claim 11  in a sample derived from a host.    
     
     
         19 . A method for identifying a compound which inhibits the action of the polypeptide of  claim 11  comprising: 
 combining DNA, hTopI-α and a potential compound under effective conditions to allow for the polypeptide to act on the DNA; and  
 determining if the compound effectively blocks the action of hTopI-α.  
 
     
     
         20 . A compound identified by the method of claim  19 .