RGD Reference Report - A role of basic residues and the putative intercalating phenylalanine of the HMG-1 box B in DNA supercoiling and binding to four-way DNA junctions.

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A role of basic residues and the putative intercalating phenylalanine of the HMG-1 box B in DNA supercoiling and binding to four-way DNA junctions.
Authors:	Stros, M Muselikova, E
Citation:	Stros M and Muselikova E, J Biol Chem. 2000 Nov 17;275(46):35699-707.
RGD ID:	8554262
Pubmed:	PMID:10962007 (View Abstract at PubMed)
DOI:	DOI:10.1074/jbc.M007167200 (Journal Full-text)
HMG (high mobility group) 1 is a chromosomal protein with two homologous DNA-binding domains, the HMG boxes A and B. HMG-1, like its individual HMG boxes, can recognize structural distortion of DNA, such as four-way DNA junctions (4WJs), that are very likely to have features common to their natural, yet unknown, cellular binding targets. HMG-1 can also bend/loop DNA and introduce negative supercoils in the presence of topoisomerase I in topologically closed DNAs. Results of our gel shift assays demonstrate that mutation of Arg(97) within the extended N-terminal strand of the B domain significantly (>50-fold) decreases affinity of the HMG box for 4WJs and alters the mode of binding without changing the structural specificity for 4WJs. Several basic amino acids of the extended N-terminal strand (Lys(96)/Arg(97)) and helix I (Arg(110)/Lys(114)) of the B domain participate in DNA binding and supercoiling. The putative intercalating hydrophobic Phe(103) of helix I is important for DNA supercoiling but dispensable for binding to supercoiled DNA and 4WJs. We conclude that the B domain of HMG-1 can tolerate substitutions of a number of amino acid residues without abolishing the structure-specific recognition of 4WJs, whereas mutations of most of these residues severely impair the topoisomerase I-mediated DNA supercoiling and change the sign of supercoiling from negative to positive.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Hmgb1	Rat	DNA geometric change	acts_upstream_of_or_within	IDA		PMID:10962007	MGI

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Hmgb1	Rat	bent DNA binding	enables	IDA		PMID:10962007	MGI
Hmgb1	Rat	crossed form four-way junction DNA binding	enables	IDA		PMID:10962007	MGI
Hmgb1	Rat	open form four-way junction DNA binding	enables	IDA		PMID:10962007	MGI

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Genes (Rattus norvegicus)

Hmgb1 (high mobility group box 1)

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A role of basic residues and the putative intercalating phenylalanine of the HMG-1 box B in DNA supercoiling and binding to four-way DNA junctions.