Seminars and Symposia
IDAC Seminar, 8 May 2014
|Secretariat, Alumni Association, IDAC|
|Date||Thursday, 8 May 2014, 17:30～|
|Room||Seminar-shitsu 1, IDAC Research building 7F|
|Title||The impact of chromatin remodeling on binding site choice and outcome of DNA double- strand break repair at the nuclear periphery|
|Affiliation||Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland|
|Person-in-charge||Kozo Tanaka Department of Molecular Oncology (ex:8491)|
|Abstract||Persistent DNA double strand beaks (DSBs) are recruited to the nuclear periphery in budding yeast. Both the Nup84 nuclear pore subcomplex and Mps3, an inner nuclear membrane SUN-domain protein, bind DSBs and are thought to act as scaffolds for repair. Here we show that two closely related chromatin remodelling complexes, SWR1 and INO80, regulate the choice of perinuclear binding sites for DSBs. The SWR1-dependent incorporation of Htz1 (H2A.Z) is essential for break relocation to both pores and Mps3 in G1- and S-phase cells, while loss of the chromatin remodeler INO80 or of Rad51 ablates binding to Mps3, in S/G2-phase only. Nuclear pore association occurs independently of cell-cycle phase, requiring neither INO80 nor Rad51. Intriguingly, disruption of the Nup84 subcomplex does not affect binding to Mps3, although loss of the Mps3 N-terminus compromises DSB relocation to pores. Importantly, functional assays indicate that the two sites favour distinct repair functions.
At the end of the talk, an idea for a novel single molecule superresolution microscopy using bicyclic peptidic binders will be introduced.