Literature DB >> 6419736

Coordinate inhibition of DNA synthesis and thymidylate synthase activity following DNA damage and repair.

R J Boorstein, A B Pardee.   

Abstract

Two agents, 3-aminobenzamide (3-AB) and beta lapachone, that inhibit repair of mammalian cell DNA damaged by methyl methane sulfonate (MMS), also coordinately blocked both DNA replication (incorporation of 3H-thymidine) and thymidylate synthase (TS) activity. Aphidicolin also inhibited both 3H-TDR incorporation and TS in damaged cells, the former more strongly than the latter, in a manner not coordinated with lethality. It is proposed that the DNA lesions created by MMS and modified by repair inhibit semiconservative DNA synthesis by allosterically interacting with the DNA replication replitase complex, so as to block its overall function and also the activity of TS, one of its enzymes.

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Year:  1983        PMID： 6419736     DOI： 10.1016/0006-291x(83)91536-x

Source DB:  PubMed          Journal:  Biochem Biophys Res Commun        ISSN： 0006-291X            Impact factor:   3.322


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