High mobility group proteins 1 and 2 recognize chromium-damaged DNA.
Chromium (Cr) is a human carcinogen and a potent DNA damaging agent. Incubation of DNA with CrCl3 resulted in dose-dependent binding of Cr to DNA and, at concentrations >20 microM, altered the electrophoretic mobility of a 100 bp oligonucleotide. We also demonstrate that high mobility group (HMG) proteins 1 and 2 bind Cr-damaged DNA (Cr-DNA). Protein binding was lesion density-dependent, with maximal binding to DNA treated with 100 microM CrCl3. HMG2 binds to Cr-DNA with a calculated Kd of approximately 10(-9) M. These proteins also bound DNA obtained from chromate-treated cells. These results suggest that the covalent attachment of Cr to DNA induces alterations in DNA structure which are recognized by HMG1 and HMG2. Therefore, these proteins may function as Cr-damaged DNA recognition proteins in vivo and as a consequence of binding, may play a role in directing the cellular response to Cr-DNA adduct formation.
Wang
J F
JF
Department of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia 19104-6002, USA.
Bashir
M
M
Engelsberg
B N
BN
Witmer
C
C
Rozmiarek
H
H
Billings
P C
PC
D000818:Animals; D002417:Cattle; D002712:Chlorides / Q000378:metabolism / Q000633:toxicity*; D002857:Chromium / Q000378:metabolism / Q000633:toxicity*; D017608:Chromium Compounds / Q000378:metabolism / Q000633:toxicity*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism; D018736:DNA Adducts / Q000378:metabolism*; D004249:DNA Damage; D018922:HL-60 Cells; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans
D002712:Chlorides; D017608:Chromium Compounds; D018736:DNA Adducts; D006609:High Mobility Group Proteins; D002857:Chromium; D004247:DNA; C017133:chromous chloride