Matches in SemOpenAlex for { <https://semopenalex.org/work/W4289968706> ?p ?o ?g. }
- W4289968706 endingPage "1264" @default.
- W4289968706 startingPage "1252" @default.
- W4289968706 abstract "Nucleotide metabolism supports RNA synthesis and DNA replication to enable cell growth and division. Nucleotide depletion can inhibit cell growth and proliferation, but how cells sense and respond to changes in the relative levels of individual nucleotides is unclear. Moreover, the nucleotide requirement for biomass production changes over the course of the cell cycle, and how cells coordinate differential nucleotide demands with cell cycle progression is not well understood. Here we find that excess levels of individual nucleotides can inhibit proliferation by disrupting the relative levels of nucleotide bases needed for DNA replication and impeding DNA replication. The resulting purine and pyrimidine imbalances are not sensed by canonical growth regulatory pathways like mTORC1, Akt and AMPK signalling cascades, causing excessive cell growth despite inhibited proliferation. Instead, cells rely on replication stress signalling to survive during, and recover from, nucleotide imbalance during S phase. We find that ATR-dependent replication stress signalling is activated during unperturbed S phases and promotes nucleotide availability to support DNA replication. Together, these data reveal that imbalanced nucleotide levels are not detected until S phase, rendering cells reliant on replication stress signalling to cope with this metabolic problem and disrupting the coordination of cell growth and division." @default.
- W4289968706 created "2022-08-06" @default.
- W4289968706 creator A5006827088 @default.
- W4289968706 creator A5006842434 @default.
- W4289968706 creator A5011534979 @default.
- W4289968706 creator A5011633717 @default.
- W4289968706 creator A5020220514 @default.
- W4289968706 creator A5035673694 @default.
- W4289968706 creator A5041429014 @default.
- W4289968706 creator A5043628221 @default.
- W4289968706 creator A5091208710 @default.
- W4289968706 date "2022-08-01" @default.
- W4289968706 modified "2023-10-18" @default.
- W4289968706 title "Nucleotide imbalance decouples cell growth from cell proliferation" @default.
- W4289968706 cites W1553978925 @default.
- W4289968706 cites W1855851918 @default.
- W4289968706 cites W1965429549 @default.
- W4289968706 cites W1971558110 @default.
- W4289968706 cites W1973245894 @default.
- W4289968706 cites W1974913955 @default.
- W4289968706 cites W1982789056 @default.
- W4289968706 cites W1996435746 @default.
- W4289968706 cites W2000144783 @default.
- W4289968706 cites W2007458878 @default.
- W4289968706 cites W2009069048 @default.
- W4289968706 cites W2024074032 @default.
- W4289968706 cites W2026170688 @default.
- W4289968706 cites W2045074917 @default.
- W4289968706 cites W2055302782 @default.
- W4289968706 cites W2061197983 @default.
- W4289968706 cites W2069571430 @default.
- W4289968706 cites W2070710923 @default.
- W4289968706 cites W2073031672 @default.
- W4289968706 cites W2083158919 @default.
- W4289968706 cites W2104961626 @default.
- W4289968706 cites W2128252882 @default.
- W4289968706 cites W2141689006 @default.
- W4289968706 cites W2153466677 @default.
- W4289968706 cites W2154141161 @default.
- W4289968706 cites W2162643935 @default.
- W4289968706 cites W2173456459 @default.
- W4289968706 cites W2258318060 @default.
- W4289968706 cites W2330335659 @default.
- W4289968706 cites W2510258949 @default.
- W4289968706 cites W2512348618 @default.
- W4289968706 cites W2520159331 @default.
- W4289968706 cites W2586265133 @default.
- W4289968706 cites W2615641945 @default.
- W4289968706 cites W2625452721 @default.
- W4289968706 cites W2706229700 @default.
- W4289968706 cites W2743992255 @default.
- W4289968706 cites W2765356256 @default.
- W4289968706 cites W2785892239 @default.
- W4289968706 cites W2802607746 @default.
- W4289968706 cites W2808014636 @default.
- W4289968706 cites W2888068269 @default.
- W4289968706 cites W2913011480 @default.
- W4289968706 cites W2938629106 @default.
- W4289968706 cites W2950983102 @default.
- W4289968706 cites W2952759348 @default.
- W4289968706 cites W2973847049 @default.
- W4289968706 cites W2982580474 @default.
- W4289968706 cites W2988589164 @default.
- W4289968706 cites W2999421965 @default.
- W4289968706 cites W3005273965 @default.
- W4289968706 cites W3024537899 @default.
- W4289968706 cites W3030498015 @default.
- W4289968706 cites W3037065298 @default.
- W4289968706 doi "https://doi.org/10.1038/s41556-022-00965-1" @default.
- W4289968706 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35927450" @default.
- W4289968706 hasPublicationYear "2022" @default.
- W4289968706 type Work @default.
- W4289968706 citedByCount "30" @default.
- W4289968706 countsByYear W42899687062021 @default.
- W4289968706 countsByYear W42899687062022 @default.
- W4289968706 countsByYear W42899687062023 @default.
- W4289968706 crossrefType "journal-article" @default.
- W4289968706 hasAuthorship W4289968706A5006827088 @default.
- W4289968706 hasAuthorship W4289968706A5006842434 @default.
- W4289968706 hasAuthorship W4289968706A5011534979 @default.
- W4289968706 hasAuthorship W4289968706A5011633717 @default.
- W4289968706 hasAuthorship W4289968706A5020220514 @default.
- W4289968706 hasAuthorship W4289968706A5035673694 @default.
- W4289968706 hasAuthorship W4289968706A5041429014 @default.
- W4289968706 hasAuthorship W4289968706A5043628221 @default.
- W4289968706 hasAuthorship W4289968706A5091208710 @default.
- W4289968706 hasBestOaLocation W42899687061 @default.
- W4289968706 hasConcept C104317684 @default.
- W4289968706 hasConcept C104690221 @default.
- W4289968706 hasConcept C1491633281 @default.
- W4289968706 hasConcept C29537977 @default.
- W4289968706 hasConcept C41141232 @default.
- W4289968706 hasConcept C512185932 @default.
- W4289968706 hasConcept C54355233 @default.
- W4289968706 hasConcept C552990157 @default.
- W4289968706 hasConcept C62112901 @default.
- W4289968706 hasConcept C73573662 @default.
- W4289968706 hasConcept C85813293 @default.