DNA modifying enzyme site locating mechanisms are dictated by biological roles: evidence for intersegmental transfer (549.1)

Abstract

DNA binding and modifying proteins, such as transcription factors, repair enzymes, restriction endonucleases, and DNA methyltransferases must find their recognition sites quickly and efficiently --although passively -- despite an overwhelming excess of non-specific DNA. A comparative study of several proteins shows that the highly distinct search mechanisms are driven by different biological contexts. For example, DNA adenine methyltransferase (Dam) utilizes intersegmental transfer, where the enzyme travels between distal regions of DNA (~600 bp), facilitated by DNA loop formation (Figure). This is the first report that this mechanism contributes to the search process for any protein, and this mechanism is consistent with Dam’s biological roles. EcoRI endonuclease, in contrast, uses a sliding mechanism, where the enzyme redundantly searches local regions of the DNA. We show that EcoRI can use this sliding mechanism to travel large distances along DNA (~300 bp). Dam travels between recognition sites freely...