| Literature DB >> 29053958 |
Satoshi Ishiyama1, Atsuya Nishiyama2, Yasushi Saeki3, Kei Moritsugu4, Daichi Morimoto5, Luna Yamaguchi6, Naoko Arai3, Rumie Matsumura1, Toru Kawakami7, Yuichi Mishima8, Hironobu Hojo7, Shintaro Shimamura9, Fuyuki Ishikawa10, Shoji Tajima8, Keiji Tanaka3, Mariko Ariyoshi5, Masahiro Shirakawa5, Mitsunori Ikeguchi4, Akinori Kidera4, Isao Suetake11, Kyohei Arita12, Makoto Nakanishi13.
Abstract
The proper location and timing of Dnmt1 activation are essential for DNA methylation maintenance. We demonstrate here that Dnmt1 utilizes two-mono-ubiquitylated histone H3 as a unique ubiquitin mark for its recruitment to and activation at DNA methylation sites. The crystal structure of the replication foci targeting sequence (RFTS) of Dnmt1 in complex with H3-K18Ub/23Ub reveals striking differences to the known ubiquitin-recognition structures. The two ubiquitins are simultaneously bound to the RFTS with a combination of canonical hydrophobic and atypical hydrophilic interactions. The C-lobe of RFTS, together with the K23Ub surface, also recognizes the N-terminal tail of H3. The binding of H3-K18Ub/23Ub results in spatial rearrangement of two lobes in the RFTS, suggesting the opening of its active site. Actually, incubation of Dnmt1 with H3-K18Ub/23Ub increases its catalytic activity in vitro. Our results therefore shed light on the essential role of a unique ubiquitin-binding module in DNA methylation maintenance.Entities:
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Year: 2017 PMID： 29053958 DOI： 10.1016/j.molcel.2017.09.037
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970