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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Li Y,Yao CF,Xu FJ,Qu YY,Li JT,Lin Y,Cao ZL,Lin PC,Xu W,Zhao SM,Zhao JY

doi

10.1038/s41467-019-10375-x

subject

Has Abstract

pub_date

2019-06-07 00:00:00

pages

2502

issue

1

issn

2041-1723

pii

10.1038/s41467-019-10375-x

journal_volume

10

pub_type

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