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Figure 1.
Histone adducts occur at H3M120 and H4M84, and DNA adduct
sites are numbered for cisPt (1, 5–7) and oxPt (1–4, 8, 9).
The central base pair at the NCP pseudo two-fold symmetry axis
is denoted by a red arrow. An apostrophe indicates the opposing
NCP half. (a–c) Anomalous difference maps, contoured at 4 (a),
4.1 (b)
and 3.4 (c)
and superimposed on the refined models for 48-h oxPt (a,b) and
cisPt (c) treatments, show platinum atom locations (black mesh).
(a) View of a thin slice of the NCP. DNA strands are colored
orange/cyan and histone proteins are colored blue (H3), green
(H4), yellow (H2A) and red (H2B). (b) An oxPt-AG adduct. (c)
cisPt adducts at GA and methionine in the NCP center. (d) DNA
sequence and adduct sites (underlined) for 79 of 147 base pairs.
(e) Summary of cisPt and oxPt adduct sites, with approximately
one NCP half shown. Methionine sites are circled, and magenta
arrows show corresponding locations in the opposing NCP half.
DNA strands and histone proteins are colored as in a. (d,e)
Bases (b) with major versus minor groove facing inward toward
the histone octamer are colored, respectively, black and orange
(d) or black and white (e). (f) Model of an oxPt adduct at the
NCP center. An oxPt-GG adduct from the oligonucleotide crystal
structure^17 was modified to an oxPt-GA adduct and superimposed
onto the oxPt1 site adjacent to the central base pair in the
high-resolution NCP crystal structure^12. The platinum (magenta)
and diaminocyclohexane atoms are shown in space-filling
representation to emphasize potential interactions with histone
elements, such as H3K115 and H3K115' (black arrows). The atomic
coordinates and structure factors for cisPt- and oxPt-treated
NCP were deposited in the Protein Data Bank under accession
codes 3B6F and 3B6G, respectively.
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