Sensitizing Cancer Cells: Is It Really All about U?

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Sensitizing Cancer Cells: Is It Really All about U? Patrick J. Stover, Robert S. Weiss Cancer Cell Volume 22, Issue 1, Pages 3-4 (July 2012) DOI: 10.1016/j.ccr.2012.06.010 Copyright © 2012 Elsevier Inc. Terms and Conditions

Figure 1 TMPK Co-Localizes with RNR at DNA Repair Sites to Limit Uracil Incorporation during DNA Synthesis (A) Under normal conditions, a low dUTP:dTTP ratio is maintained in part through the breakdown of dUTP by dUTPase (dotted arrow) and TMPK-dependent dTTP biosynthesis. (B) When TMPK is inhibited, such as by the small molecule YMU1, dTTP levels drop, resulting in a high dUTP:dTTP ratio that promotes uracil incorporation into DNA. Uracils in DNA are then targeted by uracil DNA glycosylase and excised, leading to futile repair cycles and DNA breakage (not shown). RNR, ribonucleotide reductase; TMPK, thymidylate kinase; TS, thymidylate synthase. Cancer Cell 2012 22, 3-4DOI: (10.1016/j.ccr.2012.06.010) Copyright © 2012 Elsevier Inc. Terms and Conditions