6IIW

Crystal structure of human UHRF1 PHD finger in complex with PAF15

Summary for 6IIW

• Entry DOI: 10.2210/pdb6iiw/pdb
• Descriptor: E3 ubiquitin-protein ligase UHRF1, PCNA-associated factor, ZINC ION, ... (5 entities in total)
• Functional Keywords: dna methylation, histone modification, replication, ligase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 9532.23

Authors

Arita, K.,Kori, S. (deposition date: 2018-10-07, release date: 2019-10-09, Last modification date: 2023-11-22)

Primary citation

Nishiyama, A.,Mulholland, C.B.,Bultmann, S.,Kori, S.,Endo, A.,Saeki, Y.,Qin, W.,Trummer, C.,Chiba, Y.,Yokoyama, H.,Kumamoto, S.,Kawakami, T.,Hojo, H.,Nagae, G.,Aburatani, H.,Tanaka, K.,Arita, K.,Leonhardt, H.,Nakanishi, M.
Two distinct modes of DNMT1 recruitment ensure stable maintenance DNA methylation.
Nat Commun, 11:1222-1222, 2020

PubMed Abstract: Stable inheritance of DNA methylation is critical for maintaining differentiated phenotypes in multicellular organisms. We have recently identified dual mono-ubiquitylation of histone H3 (H3Ub2) by UHRF1 as an essential mechanism to recruit DNMT1 to chromatin. Here, we show that PCNA-associated factor 15 (PAF15) undergoes UHRF1-dependent dual mono-ubiquitylation (PAF15Ub2) on chromatin in a DNA replication-coupled manner. This event will, in turn, recruit DNMT1. During early S-phase, UHRF1 preferentially ubiquitylates PAF15, whereas H3Ub2 predominates during late S-phase. H3Ub2 is enhanced under PAF15 compromised conditions, suggesting that H3Ub2 serves as a backup for PAF15Ub2. In mouse ES cells, loss of PAF15Ub2 results in DNA hypomethylation at early replicating domains. Together, our results suggest that there are two distinct mechanisms underlying replication timing-dependent recruitment of DNMT1 through PAF15Ub2 and H3Ub2, both of which are prerequisite for high fidelity DNA methylation inheritance.

PubMed: 32144273
DOI: 10.1038/s41467-020-15006-4

Experimental method

X-RAY DIFFRACTION (1.699 Å)