APC/CCDH1 synchronizes ribose-5-phosphate levels and DNA synthesis to cell cycle progression

Yang Li, Cui-Fang Yao, Fu-Jiang Xu, Yuan-Yuan Qu, Jia-Tao Li, Yan Lin, Zhong-Lian Cao, Peng-Cheng Lin, Wei Xu, Shi-Min Zhao () and Jian-Yuan Zhao ()
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Yang Li: Fudan University
Cui-Fang Yao: Fudan University
Fu-Jiang Xu: Fudan University
Yuan-Yuan Qu: Fudan University
Jia-Tao Li: Fudan University
Yan Lin: Fudan University
Zhong-Lian Cao: Fudan University
Peng-Cheng Lin: Qinghai University for Nationalities
Wei Xu: Fudan University
Shi-Min Zhao: Fudan University
Jian-Yuan Zhao: Fudan University

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract Accumulation of nucleotide building blocks prior to and during S phase facilitates DNA duplication. Herein, we find that the anaphase-promoting complex/cyclosome (APC/C) synchronizes ribose-5-phosphate levels and DNA synthesis during the cell cycle. In late G1 and S phases, transketolase-like 1 (TKTL1) is overexpressed and forms stable TKTL1-transketolase heterodimers that accumulate ribose-5-phosphate. This accumulation occurs by asymmetric production of ribose-5-phosphate from the non-oxidative pentose phosphate pathway and prevention of ribose-5-phosphate removal by depleting transketolase homodimers. In the G2 and M phases after DNA synthesis, expression of the APC/C adaptor CDH1 allows APC/CCDH1 to degrade D-box-containing TKTL1, abrogating ribose-5-phosphate accumulation by TKTL1. TKTL1-overexpressing cancer cells exhibit elevated ribose-5-phosphate levels. The low CDH1 or high TKTL1-induced accumulation of ribose-5-phosphate facilitates nucleotide and DNA synthesis as well as cell cycle progression in a ribose-5-phosphate-saturable manner. Here we reveal that the cell cycle control machinery regulates DNA synthesis by mediating ribose-5-phosphate sufficiency.

Date: 2019
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DOI: 10.1038/s41467-019-10375-x

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