CHEK1 phosphorylates E2F6

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.

CHEK1（Chk1）在应对复制压力（停滞的复制叉）时由ATR激活，其在丝氨酸残基S12上磷酸化E2F6，并可能也在丝氨酸残基S52上磷酸化。由CHEK1介导的磷酸化作用阻止了E2F6与其靶启动子的结合，从而允许转录E2F靶基因，这些基因的表达对于停滞复制叉的解决和DNA合成的重新启动是必需的。由于CHEK1的抑制或E2F6的高表达，无法诱导E2F靶基因的转录，导致复制压力引发的DNA损伤（Bertoli等人，2013年，Bertoli等人，2016年）。关于CHEK1是否在E2F6与TFDP1/TFDP2形成的复合体背景下磷酸化E2F6，尚未明确。