Meta-Biol

• Pathways

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.