High-affinity binding of tumor-suppressor protein p53 and HMGB1
to hemicatenated DNA loops.

J 2004

High-affinity binding of tumor-suppressor protein p53 and HMGB1 to hemicatenated DNA loops.

ŠTROS, Michal, Eva POLANSKÁ, Šárka POSPÍŠILOVÁ and F STRAUSS

Basic information

Original name

High-affinity binding of tumor-suppressor protein p53 and HMGB1 to hemicatenated DNA loops.

Authors

ŠTROS, Michal, Eva POLANSKÁ, Šárka POSPÍŠILOVÁ and F STRAUSS

Edition

Biochemistry, 2004

Other information

Type of outcome

Článek v odborném periodiku

Confidentiality degree

není předmětem státního či obchodního tajemství

Organization unit

Faculty of Medicine

UT WoS

000221807500040

Keywords (in Czech)

p53

Keywords in English

p53

Abstract

V originále

We have recently observed that chromatin architectural protein HMGB1 (previously reported to be involved in numerous biological processes such as DNA replication, recombination, repair, tumor growth, and metastasis) could bind with extremely high affinity (K(d) < 1 pM) to a novel DNA structure that forms a DNA loop maintained at its base by a hemicatenane (hcDNA). The loop of hcDNA contains a track of repetitive sequences derived from CA-microsatellites. Here, we report using a gel-retardation assay that tumor-suppressor protein p53 can also bind to hcDNA. p53 is a crucial molecule protecting cells from malignant transformation by regulating cell-cycle progression, apoptosis, and DNA repair by activation or repression of transcription of its target genes by binding to specific p53 DNA-binding sites and/or certain types of DNA lesions or alternative DNA structures. The affinity of p53 for hcDNA (containing sequences with no resemblance to the p53 DNA consensus sequence) is >40-fold higher (K(d) approximately 0.5 nM) than that for its natural specific binding sites within its target genes (Mdm2 promoter). Binding of p53 to hcDNA remains detectable in the presence of up to approximately 4 orders of magnitude of mass excess of competitor linear DNA, suggesting a high specificity of the interaction. p53 displays a higher affinity for hcDNA than for DNA minicircles (lacking functional p53-specific binding sequence) with a size similar to that of the loop within the hcDNA, indicating that the extreme affinity of p53 for hcDNA is likely due to the binding of the protein to the hemicatenane. Although binding of p53 to hcDNA occurs in the absence of the nonspecific DNA-binding extreme carboxy-terminal regulatory domain (30-C, residues 363-393), the isolated 30-C domain (but not the sequence-specific p53 "core domain", residues 94-312) can also bind hcDNA. Only the full-length p53 can form stable ternary complexes with hcDNA and HMGB1. The possible biological relevance of p53 and HMGB1 binding to hemicatenanes is discussed.

Citovat

ŠTROS, Michal, Eva POLANSKÁ, Šárka POSPÍŠILOVÁ and F STRAUSS. High-affinity binding of tumor-suppressor protein p53 and HMGB1 to hemicatenated DNA loops. Biochemistry. 2004, vol. 43, p. 7215-7225.

@article{838161,
   author = {Štros, Michal and Polanská, Eva and Pospíšilová, Šárka and Strauss, F},
   keywords = {p53},
   journal = {Biochemistry},
   title = {High-affinity binding of tumor-suppressor protein p53 and HMGB1 to hemicatenated DNA loops.},
   volume = {43},
   year = {2004}
}

TY  - JOUR
ID  - 838161
AU  - Štros, Michal - Polanská, Eva - Pospíšilová, Šárka - Strauss, F
PY  - 2004
TI  - High-affinity binding of tumor-suppressor protein p53 and HMGB1 to hemicatenated DNA loops.
JF  - Biochemistry
VL  - 43
SP  - 7215-7225
EP  - 7215-7225
KW  - p53
N2  - We have recently observed that chromatin architectural protein HMGB1 (previously reported to be involved in numerous biological processes such as DNA replication, recombination, repair, tumor growth, and metastasis) could bind with extremely high affinity (K(d) < 1 pM) to a novel DNA structure that forms a DNA loop maintained at its base by a hemicatenane (hcDNA). The loop of hcDNA contains a track of repetitive sequences derived from CA-microsatellites. Here, we report using a gel-retardation assay that tumor-suppressor protein p53 can also bind to hcDNA. p53 is a crucial molecule protecting cells from malignant transformation by regulating cell-cycle progression, apoptosis, and DNA repair by activation or repression of transcription of its target genes by binding to specific p53 DNA-binding sites and/or certain types of DNA lesions or alternative DNA structures. The affinity of p53 for hcDNA (containing sequences with no resemblance to the p53 DNA consensus sequence) is >40-fold higher (K(d) approximately 0.5 nM) than that for its natural specific binding sites within its target genes (Mdm2 promoter). Binding of p53 to hcDNA remains detectable in the presence of up to approximately 4 orders of magnitude of mass excess of competitor linear DNA, suggesting a high specificity of the interaction. p53 displays a higher affinity for hcDNA than for DNA minicircles (lacking functional p53-specific binding sequence) with a size similar to that of the loop within the hcDNA, indicating that the extreme affinity of p53 for hcDNA is likely due to the binding of the protein to the hemicatenane. Although binding of p53 to hcDNA occurs in the absence of the nonspecific DNA-binding extreme carboxy-terminal regulatory domain (30-C, residues 363-393), the isolated 30-C domain (but not the sequence-specific p53 "core domain", residues 94-312) can also bind hcDNA. Only the full-length p53 can form stable ternary complexes with hcDNA and HMGB1. The possible biological relevance of p53 and HMGB1 binding to hemicatenanes is discussed.
ER  -

ŠTROS, Michal, Eva POLANSKÁ, Šárka POSPÍŠILOVÁ and F STRAUSS. High-affinity binding of tumor-suppressor protein p53 and HMGB1 to hemicatenated DNA loops. \textit{Biochemistry}. 2004, vol.~43, p.~7215-7225.

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