Independent functions of DNMT1 and USP7 at replication foci

Epigenetics & Chromatin
Olya YarychkivskaTimothy H Bestor

Abstract

It has been reported that USP7 (ubiquitin-specific protease 7) prevents ubiquitylation and degradation of DNA methyltransferase 1 (DNMT1) by direct binding of USP7 to the glycine-lysine (GK) repeats that join the N-terminal regulatory domain of DNMT1 to the C-terminal methyltransferase domain. The USP7-DNMT1 interaction was reported to be mediated by acetylation of lysine residues within the (GK) repeats. 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.

References

Nov 12, 1996·Proceedings of the National Academy of Sciences of the United States of America·K L TuckerR Jaenisch
Mar 9, 2002·Molecular and Cellular Biology·Detlev BiniszkiewiczRudolf Jaenisch
Oct 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Feng Ding, J Richard Chaillet
Jun 15, 2005·Annual Review of Biochemistry·Mary Grace Goll, Timothy H Bestor
Mar 21, 2007·Molecular and Cellular Biology·Marc Damelin, Timothy H Bestor
Aug 4, 2007·Science·Magnolia BostickSteven E Jacobsen
Dec 15, 2010·Nature Structural & Molecular Biology·Pierre-Olivier EstèveSriharsa Pradhan
Jan 27, 2011·Journal of Cellular Biochemistry·Weihua QinFabio Spada
Feb 26, 2011·Cell Death and Differentiation·N KonW Gu
Apr 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kohei TakeshitaShoji Tajima
Sep 14, 2011·Methods in Molecular Biology·Mohsen KarimiTomas J Ekström
Nov 6, 2013·Molecular and Cellular Biology·Madhav JagannathanLori Frappier
May 12, 2015·Nature Communications·Jingdong ChengYanhui Xu
Jun 14, 2015·Journal of Molecular Biology·Zhi-Min ZhangJikui Song
Mar 8, 2016·Nature Structural & Molecular Biology·Emilio LeconaOscar Fernandez-Capetillo
Mar 2, 2017·Scientific Reports·Luna YamaguchiMakoto Nakanishi

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Citations

Oct 21, 2018·The Journal of Biological Chemistry·Olya YarychkivskaTimothy H Bestor
Dec 10, 2019·Annual Review of Biochemistry·Zhiyuan Chen, Yi Zhang
Aug 30, 2018·Biochemical Society Transactions·Humaira Gowher, Albert Jeltsch
Dec 14, 2018·Genes·Wendan RenJikui Song
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Gabrielle J VallesNicholas W Ashton
Dec 11, 2020·Nucleic Acids Research·Nataliya PetrykPierre-Antoine Defossez
Nov 20, 2020·International Journal of Molecular Sciences·Sol-Bi ShinHyungshin Yim
Mar 7, 2020·Trends in Immunology·Blanca T Gutierrez-DiazPanagiotis Ntziachristos
Mar 22, 2019·Current Opinion in Cell Biology·Radhika RawatPanagiotis Ntziachristos

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Methods Mentioned

BETA
acetylation
transfection
PCR
Methylation Assay
immunoprecipitation

Software Mentioned

R
ImageJ
LUMA

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