Sep 24, 2020
Histone degradation after DNA damage enhances repair
Sep 8, 2020
LifeTime - Researchers partner to improve European healthcare
Sep 3, 2020
Susan Gasser, optimist emeritus
Jun 30, 2020
Wir müssen Frauen in den Wissenschaften sichtbar machen (Deutsch)
Jun 30, 2020
We must make women more visible in the sciences (English)
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Susan M. Gasser
Genome organization during differentiation and stress
The Gasser laboratory studies how chromatin, a complex of proteins and nucleic acids, impinges on mechanisms of DNA repair and replication, and on the epigenetic inheritance of cell fate decisions. We use high throughput time-lapse imaging to address questions of chromatin folding in living organisms. With respect to stem cell determination and epigenetic inheritance, we exploit the nematode C. elegans to study the effects of 3D chromatin organization during organismal development. We examine how the environment alters that program and we ask if these changes are epigenetically inherited from one stage of life to another. With respect to the mechanisms of repair, the budding yeast, S. cerevisiae provides a flexible genetic system that allows us to model DNA folding based on the spatial dynamics of chromosomal loci.
Specific areas of focus include:
1. Nuclear subcompartments: Transient long-range interactions within active, or potentially active, chromatin (TADs) and the more stable "condensates" of heterochromatin (LADs) drive chromatin organization in the nucleus. We use genetics to identify factors that spatially segregate large chromatin domains.
2. Chromatin dynamics in repair: Chromatin organization both protects from DNA damage and facilitates repair. We focus on dynamic changes in chromatin during repair and on the role of chromatin compaction in repeat stability.
3. Stress-induced epigenetic function: We are examining whether there is a "memory" function mediated by histone post-translational modifications that controls a stress response, enhancing organismal survival. These studies have a direct impact on the treatment of medical conditions.
Susan M. Gasser
This is a list of selected publications from this group. For a full list of publications, please visit our Publications page and search by group name.
Cabianca, D.S., Munoz Jimenez, C., Kalck, V., Gaidatzis, D., Padeken, J., Seeber, A., Askjaer, P. and Gasser, S.M. (2019) Active chromatin marks drive spatial sequestration of heterochromatin in C. elegans nucleiNature, 569, 734-739.
Delaney, CE, Methot, SP, Guidi, M, Katic, I, Gasser, SM, Padeken, J. (2019) Heterochromatic foci and transcriptional repression by an unstructured MET-2/SETDB1 co-factor LIN-65J Cell Biol. 218(3), 820-838
Padeken, J., Zeller, P., Towbin, B., Katic, I., Kalck, V. and Gasser, S.M (2019) Synergistic lethality between BRCA1 and H3K9me2 loss reflects satellite derepressionGenes Dev. 33(7-8), 436-451. doi: 10.1101/gad.322495.118
Marcomini, I., Shimada, K., Delgoshaie, N., Yamamoto, I., Seeber, A., Horigome, C., Naumann, U. and Gasser, S.M. (2018) Asymmetric processing of DNA ends at double-strand breaks leads to unconstrained dynamics and ectopic translocationCell Reports, 24(10), 2614-2628.e4. doi: 10.1016/j.celrep.2018.07.102
Deshpande, I., Seeber, A., Shimada, K., Keusch, J.J., Gut, H., and Gasser, S.M. (2017) Structural basis of Mec1-Ddc2-RPA assembly and activation on single-strand DNA at sites of damageMolecular Cell, 68, 431 - 445
Amitai, A., Seeber, A., Gasser, S.M.* and Holcman, D. (2017) Visualization of chromatin decompaction and break site extrusion as predicted by statistical polymer modeling of single locus trajectoriesCell Reports, 18, 1200-1214
* Lead author
Hauer, M.H., Seeber, A., Singh, V., Thierry, R., Sack, R., Amitai, A., Kryzhanovska, M., Eglinger, J., Holcman, D., Owen-Hughes, T. and Gasser, S.M (2017) Histone degradation in response to DNA damage enhances chromatin dynamics and recombination ratesNature Struct. Mol. Biology, doi: 10.1038/nsmb.3347
Seeber, A., Hegnauer, A.M., Hustedt, N., Deshpande, I., Poli, J., Eglinger, J., Pasero, P., Gut, H., Shinohara, M., Hopfner, K-P., Shimada, K. and Gasser, S.M. (2016) RPA-mediated recruitment of MRX to forks and double-strand breaks holds sister chromatids togetherMolecular Cell, 64, 951 - 966. doi: 10.1016/j.molcel.2016.10.032
Zeller, P., Padeken, J., van Schendel, R., Kalck, V., Tijsterman, M. and Gasser, S.M. (2016) Histone H3K9 methylation is dispensable for C. elegans development, but suppresses RNA-DNA hybrid-associated repeat instabilityNature Genetics, 48, 1385 - 1395. doi: 10.1038/ng.3672
Horigome, C., Bustard, D., Marcomini, I., Tsai-Pflugfelder, M., Cobb, J.A. and Gasser, S.M. (2016) PolySUMOylation by Siz2 and Mms21 triggers relocation of DNA breaks to nuclear pores through the Slx5/Slx8 STUbLGenes & Dev. 30, 931-945
Poli, J., Gerhold, C.-B., Tosi, A., Hustedt, N., Seeber, A., Sack, R., Herzog, F., Pasero, P., Shimada, K., Hopfner, K-P. and Gasser, S.M. (2016) Mec1, INO80 and the PAF1 complex cooperate to limit transcription-replication conflicts through RNAPII removal during replication stressGenes & Dev. 30, 337-354
Gonzalez-Sandoval, A., Towbin, B.D., Kalck, V., Cabianca, D.S., Gaidatzis, D.,Hauer, M.H., Geng, L., Wang, L., Yang, T., Wang,. X., Zhao, K. and Gasser, S.M. (2015) Perinuclear Anchoring of H3K9-Methylated Chromatin Stabilizes Induced Cell Fate in C. elegans embryos.Cell, 163, 1333-1347
Hustedt H, Seeber A, Sack R, Bhupinder B, Vlaming H, van Leeuwen F, Guenole A, van Attikum H, Srivas R, Ideker T, Shimada K, Gasser SM (2015) Yeast PP4 interacts with ATR homologue Ddc2-Mec1 and regulates checkpoint signalingMol Cell. 55:273-289
Towbin BD, Gonzalez-Aguilera C, Sack R, Gaidatzis D, Kalck V, Meister P, Askjaer P, Gasser SM (2012) Step-wise methylation of histone H3K9 positions chromosome arms at the nuclear periphery in C. elegans embryosCell. 150:934-947
Dion V, Kalck V, Horigome C, Towbin BD, Gasser SM (2012) Increased dynamics of double strand breaks requires Mec1, Rad9 and the homologous recombination machineryNat Cell Biol. 14:502-509
Taddei A, Van Houwe G, Hediger F, Kalck V, Cubizolles F, Schober H, Gasser SM (2006) Nuclear pore association confers optimal expression levels for an inducible yeast geneNature 441:774-778
Full list of publications
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