Molecular mechanism underlying elevated CPD deamination at minor-in rotational settings in nucleosomes. (A) Chemical structure of a thymine–cytosine CPD. Previous studies indicate that the rate-limiting step of cytosine deamination is hydrolytic attack by a water (H₂O) molecule on the cytosine C4 position. The accessibility of these C4 position to hydrolytic attack can be quantified using the solvent accessible surface area (SASA). (B) Quantification of the SASA_C4 for cytosine bases in the yeast nucleosome structure (1ID3) for bases at minor-in or minor-out rotational settings. (**) P < 0.01 based on a Mann–Whitney U test. (C) Same as panel B, except the SASA_C4 is calculated for hydroxide (radius ∼ 1.1 Å) instead of water. (*) P < 0.05 based on a Mann–Whitney U test. (D) Chemical structure of the guanine–cytosine base pair, highlighting the fact that the cytosine C4 position is located near the major groove.