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Archived Comments for: The pemetrexed-containing treatments in the non-small cell lung cancer, is -/low thymidylate synthase expression better than +/high thymidylate synthase expression: a meta-analysis

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  1. Error in the description of the catalytic mechanism of thymidylate synthase (TS).

    Peter Wilson, University of Southern California

    21 October 2014

    In the manuscript the authors incorrectly state that the function of the enzyme thymidylate synthase (TS) as the following:

    "TS is a key enzyme that catalyzes the methylation of fluorod UMP, the precursor of DNA synthesis, into dTMP"

    This is incorrect. Thymidylate synthase catalyzes the reductive methylation of dUMP (deoxyuridine) to dTMP (thymidine monophosphate; thymidylate). Fluoro-dUMP (or FdUMP as it is more commonly abbreviated to) is a potent fluoropyrimidine-derived irreversible inhibitor of TS.

    The reference provided for the above enzymatic mechanism is also not specific to TS whatsoever and the proper terms should be given as well as the abbreviations e.g. thymidine monophosphate (dTMP) and deoxyuridine monophosphate (dUMP).

    The following reference describes, in detail, the structure and mechanism of thymidylate synthase:

    Annu Rev Biochem. 1995;64:721-62.

    The catalytic mechanism and structure of thymidylate synthase.

    Carreras CW1, Santi DV.

    The PubMed ID is 7574499

    Since the subject of this manuscript is centered around TS, the enzymatic function should be described accurately and precisely and this should be rectified.

    The authors also refer to their analysis as a 'systemic' analysis in the methods when of course it should be 'systematic'.

    Competing interests

    None declared