Details

Autor(en) / Beteiligte

• Chiapperino, Dominic
• Kroth, Heiko
• Kramarczuk, Irene H.
• Sayer, Jane M.
• Masutani, Chikahide
• Hanaoka, Fumio
• Jerina, Donald M.
• Cheh, Albert M.

Titel

Preferential Misincorporation of Purine Nucleotides by Human DNA Polymerase η Opposite Benzo[a]pyrene 7,8-Diol 9,10-Epoxide Deoxyguanosine Adducts

Ist Teil von

• The Journal of biological chemistry, 2002-04, Vol.277 (14), p.11765-11771

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• Human DNA polymerase η was used to copy four stereoisomeric deoxyguanosine (dG) adducts derived from benzo[a]pyrene 7,8-diol 9,10-epoxide (diastereomer with the 7-hydroxyl group and epoxide oxygen trans (BaP DE-2)). The adducts, formed by either cis or trans epoxide ring opening of each enantiomer of BaP DE-2 by N2 of dG, were placed at the fourth nucleotide from the 5′-end in two 16-mer sequence contexts, 5′∼CG*A∼ and 5′∼GG*T. polη was remarkably error prone at all four diol epoxide adducts, preferring to misincorporate G and A at frequencies 3- to more than 50-fold greater than the frequencies for T or the correct C, although the highest rates were 60-fold below the rate of incorporation of C opposite a non-adducted G. Anti to syn rotation of the adducted base, consistent with previous NMR data for a BaP DE-2 dG adduct placed just beyond a primer terminus, provides a rationale for preferring purine misincorporation. Extension of purine misincorporations occurred preferentially, but extension beyond the adduct site was weak with Vmax/Km values generally 10-fold less than for misincorporation. Mostly A was incorporated opposite (+)-BaP DE-2 dG adducts, which correlates with published observations that G → T is the most common type of mutation that (+)-BaP DE-2 induces in mammalian cells.