Human DNA polymerase mu (Pol mu) exhibits an unusual replication slippage ability at AAF lesion |
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Authors: | Duvauchelle Jean-Baptiste Blanco Luis Fuchs Robert P P Cordonnier Agnes M |
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Institution: | UPR9003 du CNRS, Cancérogenèse et Mutagenèse Moléculaire et Structurale, ESBS, Boulevard S. Brant, 67400 Strasbourg, France. |
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Abstract: | We analyzed the ability of various cell extracts to extend a radiolabeled primer past an N-2-acetylaminofluorene (AAF) adduct located on a primed single-stranded template. When the 3′ end of the primer is located opposite the lesion, partially fractionated human primary fibroblast extracts efficiently catalyzed primer-terminus extension by adding a ladder of about 15 dGMPs, in an apparently non-templated reaction. This activity was not detected in SV40-transformed fibroblasts or in HeLa cell extracts unless purified human DNA polymerase mu (Pol µ) was added. In contrast, purified human Pol µ alone could only add three dGMPs as predicted from the sequence of the template. These results suggest that a cofactor(s) present in cellular extracts modifies Pol µ activity. The production of the dGMP ladder at the primer terminus located opposite the AAF adduct reveals an unusual ability of Pol µ (in conjunction with its cofactor) to perform DNA synthesis from a slipped intermediate containing several unpaired bases. |
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