TY - JOUR
T1 - Human MutSα specifically binds to DNA containing aminofluorene and acetylaminofluorene adducts
AU - Li, Guo Min
AU - Wang, Huixian
AU - Romano, Louis J.
PY - 1996
Y1 - 1996
N2 - Defects in mismatch repair are associated with several types of cancer. It is also generally believed that environmental carcinogens are responsible for the initiation of cancers by the induction of mutations in critical genes. Prior genetic studies have suggested that the mismatch repair system can also recognize certain forms of DNA damage such as O6-methylguanine and UV photoproducts, and, therefore, mismatch repair may play a role in environmental agent-induced carcinogenesis. To examine this hypothesis, hMutSα, a heterodimer which consists of hMSH2 and GTBP and participates in strand-specific mismatch repair, was tested for its ability to recognize DNA containing a site-specific C8-guanine adduct of aminofluorene (AF) or N- acetyl-2-aminofluorene (AAFL). We show here that hMutSα specifically binds to both AF and AAF adducts. This binding requires both hMSH2 and GTBP. Results from competition and titration experiments indicate that the binding efficiency of hMutSα to AF and AAF is about 60% of that to a G-T mismatch, but is at least 10-fold that to an otherwise identical homoduplex DNA without the chemical modification. The specific binding of AF and AAF adducts by hMutSα suggests that strand-specific mismatch repair is involved in processing DNA damage induced by environmental carcinogens.
AB - Defects in mismatch repair are associated with several types of cancer. It is also generally believed that environmental carcinogens are responsible for the initiation of cancers by the induction of mutations in critical genes. Prior genetic studies have suggested that the mismatch repair system can also recognize certain forms of DNA damage such as O6-methylguanine and UV photoproducts, and, therefore, mismatch repair may play a role in environmental agent-induced carcinogenesis. To examine this hypothesis, hMutSα, a heterodimer which consists of hMSH2 and GTBP and participates in strand-specific mismatch repair, was tested for its ability to recognize DNA containing a site-specific C8-guanine adduct of aminofluorene (AF) or N- acetyl-2-aminofluorene (AAFL). We show here that hMutSα specifically binds to both AF and AAF adducts. This binding requires both hMSH2 and GTBP. Results from competition and titration experiments indicate that the binding efficiency of hMutSα to AF and AAF is about 60% of that to a G-T mismatch, but is at least 10-fold that to an otherwise identical homoduplex DNA without the chemical modification. The specific binding of AF and AAF adducts by hMutSα suggests that strand-specific mismatch repair is involved in processing DNA damage induced by environmental carcinogens.
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U2 - 10.1074/jbc.271.39.24084
DO - 10.1074/jbc.271.39.24084
M3 - Article
C2 - 8798646
AN - SCOPUS:0029661432
SN - 0021-9258
VL - 271
SP - 24084
EP - 24088
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 39
ER -