CHEK1 phosphorylates E2F6

Stable Identifier
R-HSA-9007539
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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CHEK1 (Chk1), activated by ATR in response to replication stress (stalled replication forks), phosphorylates E2F6 on serine residue S12 and possibly also on serine residue S52. CHEK1-mediated phosphorylation prevents association of E2F6 with its target promoters, allowing transcription of E2F target genes whose expression is needed for resolution of stalled replication forks and restart of DNA synthesis. Inability to induce transcription of E2F target genes (due to CHEK1 inhibition or E2F6 overexpression) leads to replication stress-induced DNA damage (Bertoli et al. 2013, Bertoli et al. 2016). It has not been clarified whether CHEK1 phosphorylates E2F6 in the context of the E2F6 complex with TFDP1/TFDP2.

Literature References
PubMed ID Title Journal Year
23954429 Chk1 inhibits E2F6 repressor function in response to replication stress to maintain cell-cycle transcription

Bertoli, C, Klier, S, McGowan, C, Wittenberg, C, de Bruin, RA

Curr. Biol. 2013
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Catalyst Activity
Title
protein serine/threonine kinase activity of p-S317,S345-CHEK1 [nucleoplasm]
Physical Entity
Activity
Orthologous Events
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