Nature of full-length HMGB1 binding to cisplatin-modified DNA

Cited 80 time in webofscience Cited 0 time in scopus
  • Hit : 262
  • Download : 0
HMGB1, a highly conserved non-histone DNA-binding protein, interacts with specific DNA structural motifs such as those encountered at cisplatin damage, four-way junctions, and supercoils. The interaction of full-length HMGB1, containing two tandem HMG box domains and a C-terminal acidic tail, with cisplatin-modified DNA was investigated by hydroxyl radical footprinting and electrophoretic gel mobility shift assays. The full-length HMGB1 protein binds to DNA containing a 1,2-intrastrand d(GpG) cross-link mainly through domain A, as revealed by footprinting, with a dissociation constant K-d of 120 nM. Site-directed mutagenesis of intercalating residues in both HMG domains A and B in full-length HMGB1 further supports the conclusion that only one HMG box domain is bound to the site of cisplatin damage. Interaction of the C-terminal tail with the rest of the HMGB1 protein was examined by EDC cross-linking experiments. The acidic tail mainly interacts with domain B and linker regions rather than domain A in HMGB1. These results illuminate the respective roles of the tandem HMG boxes and the C-terminal acidic tail of HMGB1 in binding to DNA and to the major DNA adducts formed by the anticancer drug cisplatin.
Publisher
AMER CHEMICAL SOC
Issue Date
2003-03
Language
English
Article Type
Article
Keywords

V(D)J RECOMBINATION; EXCISION NUCLEASE; CHROMATIN PROTEIN; CANCER-CELLS; DOMAIN; RECOGNITION; HMG-1; ADDUCTS; SEQUENCES; COMPLEXES

Citation

BIOCHEMISTRY, v.42, no.9, pp.2664 - 2671

ISSN
0006-2960
DOI
10.1021/bi026972w
URI
http://hdl.handle.net/10203/173660
Appears in Collection
CH-Journal Papers(저널논문)
Files in This Item
There are no files associated with this item.
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 80 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0