Msc1 is a nuclear envelope protein that reinforces DNA repair in late mitosis
Sara Medina-Suárez,
Jessel Ayra-Plasencia,
Lara Pérez-Martínez,
Falk Butter,
Félix Machín
Affiliations
Sara Medina-Suárez
Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain; Instituto de Tecnologías Biomédicas, Universidad de La Laguna, 38200 San Cristóbal de La Laguna, Spain
Jessel Ayra-Plasencia
Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain; Instituto de Tecnologías Biomédicas, Universidad de La Laguna, 38200 San Cristóbal de La Laguna, Spain
Lara Pérez-Martínez
Institute of Molecular Biology (IMB), 55128 Mainz, Germany
Falk Butter
Institute of Molecular Biology (IMB), 55128 Mainz, Germany; Institute of Molecular Virology and Cell Biology, Friedrich Loeffler Institute, 17493 Greifswald, Germany
Félix Machín
Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, Spain; Instituto de Tecnologías Biomédicas, Universidad de La Laguna, 38200 San Cristóbal de La Laguna, Spain; Facultad de Ciencias de la Salud, Universidad Fernando Pessoa Canarias, 35450 Las Palmas de Gran Canaria, Spain; Corresponding author
Summary: Precise double-strand break (DSB) repair is a paramount for genome stability. Homologous recombination (HR) repairs DSBs when cyclin-dependent kinase (CDK) activity is high, which correlates with the availability of the sister chromatid as a template. However, anaphase and telophase are paradoxical scenarios since high CDK favors HR despite sister chromatids being no longer aligned. To identify factors specifically involved in DSB repair in late mitosis, we have undertaken comparative proteomics in Saccharomyces cerevisiae and found that meiotic sister chromatid 1 (Msc1), a poorly characterized nuclear envelope protein, is significantly enriched upon both random and guided DSBs. We further show that Δmsc1 is more sensitive to DSBs in late mitosis, and has a delayed repair of DBSs, as indicated by increased Rad53 hyperphosphorylation, a higher presence of RPA foci, fewer Rad52 repair factories, and slower HR completion. We propose that Msc1 favors the later stages of HR and the timely completion of DSB repair before cytokinesis.
