Protein-induced DNA linking number change by sequence-specific DNA binding proteins and its biological effects
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Sequence-specific DNA-binding proteins play essential roles in many fundamental biological events such as DNA replication, recombination, and transcription. One common feature of sequence-specific DNA-binding proteins is to introduce structural changes to their DNA recognition sites including DNA-bending and DNA linking number change (ΔLk). In this article, I review recent progress in studying protein-induced ΔLk by several sequence-specific DNA-binding proteins, such as E. coli cAMP receptor protein (CRP) and lactose repressor (LacI). It was demonstrated recently that protein-induced ΔLk is an intrinsic property for sequence-specific DNA-binding proteins and does not correlate to protein-induced other structural changes, such as DNA bending. For instance, although CRP bends its DNA recognition site by 90°, it was not able to introduce a ΔLk to it. However, LacI was able to simultaneously bend and introduce a ΔLk to its DNA binding sites. Intriguingly, LacI also constrained superhelicity within LacI–lac O1 complexes if (−) supercoiled DNA templates were provided. I also discuss how protein-induced ΔLk help sequence-specific DNA-binding proteins regulate their biological functions. For example, it was shown recently that LacI utilizes the constrained superhelicity (ΔLk) in LacI-lac O1 complexes and serves as a topological barrier to constrain free, unconstrained (−) supercoils within the 401-bp DNA loop. These constrained (−) supercoils enhance LacI’s binding affinity and therefore the repression of the lac promoter. Other biological functions include how DNA replication initiators λ O and DnaA use the induced ΔLk to open/melt bacterial DNA replication origins.
KeywordsDNA linking number change (ΔLk) lac repressor (LacI) cAMP receptor protein (CRP) λ O DNA-bending DNA topological barrier
This work was supported by grants from the National Institutes of Health 1R15GM109254-01A1 (to F.L.).
Compliance with ethical standards
Conflicts of interest
Fenfei Leng declares that he has no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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