Independent functions of DNMT1 and USP7 at replication foci
O Yarychkivska, etc Epigenetics & Chromatin,
We found that DNMT1 is present at normal levels in mouse and human cells that contain undetectable levels of USP7. Substitution of the (GK) repeats by (GQ) repeats prevents lysine acetylation but does not affect the stability of DNMT1 or the ability of the mutant protein to restore genomic methylation levels when expressed in Dnmt1-null ES cells. Furthermore, both USP7 and PCNA are recruited to sites of DNA replication independently of the presence of DNMT1, and there is no evidence that DNMT1 is degraded in cycling cells after S phase.
Multiple lines of evidence indicate that homeostasis of DNMT1 in somatic cells is controlled primarily at the level of transcription and that interaction of USP7 with the (GK) repeats of DNMT1 is unlikely to play a major role in the stabilization of DNMT1 protein.