Informace o publikaci

Srs2 mediates PCNA-SUMO-dependent inhibition of DNA repair synthesis

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BURKOVICS Peter ŠEBESTA Marek SISÁKOVÁ Alexandra PLAULT Nicolas SZUKACSOV Valeria ROBERT Thomas PINTER Lajos MARINI PALOMEQUE María Victoria KOLESÁR Peter HARACSKA Lajos GANGLOFF Serge KREJČÍ Lumír

Rok publikování 2013
Druh Článek v odborném periodiku
Časopis / Zdroj EMBO JOURNAL
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Doi http://dx.doi.org/10.1038/emboj.2013.9
Obor Genetika a molekulární biologie
Klíčová slova DNA repair synthesis; genome stability; PCNA SUMOylation; Srs2; SUMO interacting motif
Přiložené soubory
Popis Completion of DNA replication needs to be ensured even when challenged with fork progression problems or DNA damage. PCNA and its modifications constitute a molecular switch to control distinct repair pathways. In yeast, SUMOylated PCNA (S-PCNA) recruits Srs2 to sites of replication where Srs2 can disrupt Rad51 filaments and prevent homologous recombination (HR). We report here an unexpected additional mechanism by which S-PCNA and Srs2 block the synthesis-dependent extension of a recombination intermediate, thus limiting its potentially hazardous resolution in association with a cross-over. This new Srs2 activity requires the SUMO interaction motif at its C-terminus, but neither its translocase activity nor its interaction with Rad51. Srs2 binding to S-PCNA dissociates Pol delta and Pol eta from the repair synthesis machinery, thus revealing a novel regulatory mechanism controlling spontaneous genome rearrangements. Our results suggest that cycling cells use the Siz1-dependent SUMOylation of PCNA to limit the extension of repair synthesis during template switch or HR and attenuate reciprocal DNA strand exchanges to maintain genome stability.
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