| In a yeast two hybrid system based on reconstitution of Ras signaling , menin was found to interact with the 32 kDa subunit ( RPA 2 ) of replication protein A ( RPA ) , a heterotrimeric protein required for DNA replication , recombination , and repair . ^^^ The menin RPA 2 interaction was confirmed in a conventional yeast two hybrid system and by direct interaction between purified proteins . ^^^ Menin RPA 2 binding was inhibited by a number of menin missense mutations found in individuals with multiple endocrine neoplasia type 1 , and the interacting regions were mapped to the N terminal portion of menin and amino acids 43 to 171 of RPA 2 . ^^^ This region of RPA 2 contains a weak single stranded DNA binding domain , but menin had no detectable effect on RPA DNA binding in vitro . ^^^ Menin bound preferentially in vitro to free RPA 2 rather than the RPA heterotrimer or a subcomplex consisting of RPA 2 bound to the 14 kDa subunit ( RPA 3 ) . ^^^ |