Mec1 Is Activated at the Onset of Normal S Phase by Low-dNTP Pools Impeding DNA Replication

Forey, Romain (author)

Poveda, Ana (author)

Sharma, Sushma (author): Umeå universitet,Institutionen för medicinsk kemi och biofysik,Molekylär Infektionsmedicin, Sverige (MIMS),Andrei Chabes

Barthe, Antoine (author)

Padioleau, Ismael (author)

Renard, Claire (author)

Lambert, Robin (author)

Skrzypczak, Magdalena (author)

Ginalski, Krzysztof (author)

Lengronne, Armelle (author)

Chabes, Andrei, Professor (author): Umeå universitet,Institutionen för medicinsk kemi och biofysik,Molekylär Infektionsmedicin, Sverige (MIMS)

Pardo, Benjamin (author)

Pasero, Philippe (author)

(creator_code:org_t)

Elsevier, 2020
2020
English.
In: Molecular Cell. - : Elsevier. - 1097-2765 .- 1097-4164. ; 78:3, s. 496-410.e4

Related links:: http://www.cell.com/...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Abstract Subject headings

The Mec1 and Rad53 kinases play a central role during acute replication stress in budding yeast. They are also essential for viability in normal growth conditions, but the signal that activates the Mec1-Rad53 pathway in the absence of exogenous insults is currently unknown. Here, we show that this pathway is active at the onset of normal S phase because deoxyribonucleotide triphosphate (dNTP) levels present in G1 phase may not be sufficient to support processive DNA synthesis and impede DNA replication. This activation can be suppressed experimentally by increasing dNTP levels in G1 phase. Moreover, we show that unchallenged cells entering S phase in the absence of Rad53 undergo irreversible fork collapse and mitotic catastrophe. Together, these data indicate that cells use suboptimal dNTP pools to detect the onset of DNA replication and activate the Mec1-Rad53 pathway, which in turn maintains functional forks and triggers dNTP synthesis, allowing the completion of DNA replication.

By the author/editor: Forey, Romain; Poveda, Ana; Sharma, Sushma; Barthe, Antoine; Padioleau, Ismae ...; Renard, Claire; show more...; Lambert, Robin; Skrzypczak, Magd ...; Ginalski, Krzysz ...; Lengronne, Armel ...; Chabes, Andrei, ...; Pardo, Benjamin; Pasero, Philippe; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Cell and Molecul ...

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