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Monitoring Homology Search during DNA Double-Strand Break Repair In Vivo

MPG-Autoren
http://pubman.mpdl.mpg.de/cone/persons/resource/persons78559

Renkawitz,  Jörg
Jentsch, Stefan / Molecular Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons96522

Lademann,  Claudio A.
Jentsch, Stefan / Molecular Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78182

Kalocsay,  Marian
Jentsch, Stefan / Molecular Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons78165

Jentsch,  Stefan
Jentsch, Stefan / Molecular Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Zitation

Renkawitz, J., Lademann, C. A., Kalocsay, M., & Jentsch, S. (2013). Monitoring Homology Search during DNA Double-Strand Break Repair In Vivo. MOLECULAR CELL, 50(2), 261-272. doi:10.1016/j.molcel.2013.02.020.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0013-B24E-A
Zusammenfassung
Homologous recombination (HR) is crucial for genetic exchange and accurate repair of DNA double-strand breaks and is pivotal for genome integrity. HR uses homologous sequences for repair, but how homology search, the exploration of the genome for homologous DNA sequences, is conducted in the nucleus remains poorly understood. Here, we use time-resolved chromatin immunoprecipitations of repair proteins to monitor homology search in vivo. We found that homology search proceeds by a probing mechanism, which commences around the break and samples preferentially on the broken chromosome. However, elements thought to instruct chromosome loops mediate homology search shortcuts, and centromeres, which cluster within the nucleus, may facilitate homology search on other chromosomes. Our study thus reveals crucial parameters for homology search in vivo and emphasizes the importance of linear distance, chromosome architecture, and proximity for recombination efficiency.