TY - JOUR
T1 - Meiotic functions of RAD18
AU - Inagaki, Akiko
AU - Sleddens-Linkels, Esther
AU - Wassenaar, Evelyne
AU - Ooms, Marja
AU - van Cappellen, Wiggert A.
AU - Hoeijmakers, Jan H.J.
AU - Seibler, Jost
AU - Vogt, Thomas F.
AU - Shin, Myung K.
AU - Grootegoed, J. Anton
AU - Baarends, Willy M.
PY - 2011/8/15
Y1 - 2011/8/15
N2 - 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.
AB - 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.
KW - DNA double-strand break repair
KW - HR6B
KW - Meiosis
KW - RAD18
KW - XY body
UR - http://www.scopus.com/inward/record.url?scp=79961145160&partnerID=8YFLogxK
U2 - 10.1242/jcs.081968
DO - 10.1242/jcs.081968
M3 - Article
C2 - 21807948
AN - SCOPUS:79961145160
SN - 0021-9533
VL - 124
SP - 2837
EP - 2850
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - 16
ER -