Meiotic functions of RAD18

Akiko Inagaki, Esther Sleddens-Linkels, Evelyne Wassenaar, Marja Ooms, Wiggert A. van Cappellen, Jan H.J. Hoeijmakers, Jost Seibler, Thomas F. Vogt, Myung K. Shin, J. Anton Grootegoed, Willy M. Baarends

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

21 Citaten (Scopus)

Samenvatting

RAD18 is an ubiquitin ligase that is involved in replication damage bypass and DNA double-strand break (DSB) repair processes in mitotic cells. Here, we investigated the testicular phenotype of Rad18-knockdown mice to determine the function of RAD18 in meiosis, and in particular, in the repair of meiotic DSBs induced by the meiosis-specific topoisomerase-like enzyme SPO11. We found that RAD18 is recruited to a specific subfraction of persistent meiotic DSBs. In addition, RAD18 is recruited to the chromatin of the XY chromosome pair, which forms the transcriptionally silent XY body. At the XY body, RAD18 mediates the chromatin association of its interaction partners, the ubiquitin-conjugating enzymes HR6A and HR6B. Moreover, RAD18 was found to regulate the level of dimethylation of histone H3 at Lys4 and maintain meiotic sex chromosome inactivation, in a manner similar to that previously observed for HR6B. Finally, we show that RAD18 and HR6B have a role in the efficient repair of a small subset of meiotic DSBs.

Originele taal-2Engels
Pagina's (van-tot)2837-2850
Aantal pagina's14
TijdschriftJournal of Cell Science
Volume124
Nummer van het tijdschrift16
DOI's
StatusGepubliceerd - 15 aug. 2011
Extern gepubliceerdJa

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