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Protein-induced DNA linking number change by sequence-specific DNA binding proteins and its biological effects

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Abstract

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.

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Acknowledgment

This work was supported by grants from the National Institutes of Health 1R15GM109254-01A1 (to F.L.).

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  1. Biomolecular Sciences Institute and Department of Chemistry & Biochemistry, Florida International University, 11200 SW 8th Street, Miami, FL, 33199, USA

    Fenfei Leng

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  1. Fenfei Leng
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Leng, F. Protein-induced DNA linking number change by sequence-specific DNA binding proteins and its biological effects. Biophys Rev 8, 197–207 (2016). https://doi.org/10.1007/s12551-016-0204-z

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  • DOI: https://doi.org/10.1007/s12551-016-0204-z

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