Independent functions of DNMT1 and USP7 at replication foci
Abstract Background 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 methyltrans...
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | Epigenetics & Chromatin |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13072-018-0179-z |
| _version_ | 1818216595383648256 |
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| author | Olya Yarychkivska Omid Tavana Wei Gu Timothy H. Bestor |
| author_facet | Olya Yarychkivska Omid Tavana Wei Gu Timothy H. Bestor |
| author_sort | Olya Yarychkivska |
| collection | DOAJ |
| description | Abstract Background 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. Results 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. Conclusions 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. |
| first_indexed | 2024-12-12T06:54:28Z |
| format | Article |
| id | doaj.art-43e53c26a665441bbe4d44e014172d86 |
| institution | Directory Open Access Journal |
| issn | 1756-8935 |
| language | English |
| last_indexed | 2024-12-12T06:54:28Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj.art-43e53c26a665441bbe4d44e014172d862022-12-22T00:33:59ZengBMCEpigenetics & Chromatin1756-89352018-02-011111910.1186/s13072-018-0179-zIndependent functions of DNMT1 and USP7 at replication fociOlya Yarychkivska0Omid Tavana1Wei Gu2Timothy H. Bestor3Department of Genetics and Development, College of Physicians and Surgeons, Columbia UniversityDepartment of Pathology and Cell Biology, Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia UniversityDepartment of Pathology and Cell Biology, Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia UniversityDepartment of Genetics and Development, College of Physicians and Surgeons, Columbia UniversityAbstract Background 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. Results 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. Conclusions 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.http://link.springer.com/article/10.1186/s13072-018-0179-zDNMT1USP7Glycine-lysine repeatsProtein stabilityReplication foci |
| spellingShingle | Olya Yarychkivska Omid Tavana Wei Gu Timothy H. Bestor Independent functions of DNMT1 and USP7 at replication foci Epigenetics & Chromatin DNMT1 USP7 Glycine-lysine repeats Protein stability Replication foci |
| title | Independent functions of DNMT1 and USP7 at replication foci |
| title_full | Independent functions of DNMT1 and USP7 at replication foci |
| title_fullStr | Independent functions of DNMT1 and USP7 at replication foci |
| title_full_unstemmed | Independent functions of DNMT1 and USP7 at replication foci |
| title_short | Independent functions of DNMT1 and USP7 at replication foci |
| title_sort | independent functions of dnmt1 and usp7 at replication foci |
| topic | DNMT1 USP7 Glycine-lysine repeats Protein stability Replication foci |
| url | http://link.springer.com/article/10.1186/s13072-018-0179-z |
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