Article
Biochemistry & Molecular Biology
Daniel S. Saxton, Jasper Rine
Summary: Genetically identical cells can have different transcriptional states. Inheritance of silenced states relies not only on the inheritance of modified histones, but also on the presence of silencers. Strong silencers recruit Sir proteins and silence the locus in all cells, while weakening silencers can result in stable silencing in some cells but with a probability of conversion to an expressed state lacking Sir protein recruitment. The presence of different silencer states and variations in silencer-bound proteins or the concentration of a structural Sir protein can modulate the probability of a locus exhibiting the silenced or expressed state.
Article
Cell Biology
Jun Liu, Xiaojing Hong, Lihui Wang, Chao-Ya Liang, Jun-Ping Liu
Summary: Telomere shortening leads to cellular senescence, and this study reveals a dual opposing control mechanism of sub-telomeric Y' element recombination by Sir3/4 and Rif1, regulating telomere length and cell senescence in yeast Saccharomyces cerevisiae. Sir4 repression of Y' element recombination is negatively regulated by Rif1, mediating senescence-evasion induced by Sir4 deficiency.
Article
Biochemistry & Molecular Biology
Francesco Abbiati, Stefano Angelo Garagnani, Ivan Orlandi, Marina Vai
Summary: Supplementation of Quercetin (QUER) in yeast cells can increase their lifespan by reducing oxidative stress and promoting anabolic metabolism, specifically gluconeogenesis, leading to an increase in trehalose, a reserve carbohydrate.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Samantha L. Sholes, Kayarash Karimian, Ariel Gershman, Thomas J. Kelly, Winston Timp, Carol W. Greider
Summary: We developed a method to tag and measure telomere length in yeast using nanopore sequencing. We observed stable chromosome-specific telomere lengths and examined the role of RIF1 and TEL1 in telomere length regulation. The study suggests the influence of Y ' elements on telomere length regulation and provides insights into possible new biological mechanisms.
Article
Microbiology
Yeong Hyeock Kim, Ji-In Ryu, Mayur Nimbadas Devare, Juhye Jung, Jeong-Yoon Kim
Summary: This study investigated the molecular mechanism underlying the altered stress susceptibilities in Saccharomyces cerevisiae due to the absence of Sir2. The absence of Sir2 increased sensitivity to H2O2 during the post-diauxic phase but increased resistance during the exponential growth phase. Transcriptome analysis revealed lower expression levels of several oxidative defense genes in the sir2 Delta strain, potentially explaining its increased susceptibility to H2O2. Interestingly, the sir2 Delta ras2 Delta double mutant exhibited greater resistance to H2O2 than the ras2 Delta single mutant, and the regulation of the cytoplasmic catalase encoded by CTT1 was critical for this increased resistance.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Multidisciplinary Sciences
Rebecca C. Young, Alexander S. Kitaysky, Hugh M. Drummond
Summary: The study found a strong positive correlation between telomere lengths among Blue-footed Booby breeding pairs, with interactions between parental telomere lengths affecting fledgling recruitment and adult survival. Having long telomeres benefits survival, while choosing a mate with long telomeres benefits reproductive output but may penalize survival.
SCIENTIFIC REPORTS
(2021)
Article
Biotechnology & Applied Microbiology
Samantha D. M. Arras, Taylor R. Hibbard, Lucy Mitsugi-McHattie, Matthew A. Woods, Charlotte E. Johnson, Andrew Munkacsi, Sylvie Hermann-Le Denmat, Austen R. D. Ganley
Summary: This study validated a simple, cheap and robust method to identify Saccharomyces cerevisiae mating types. When cells of opposite mating type are mixed in liquid media, they exhibit a 'creeping' phenotype by crawling up the culture vessel sides, which can be easily detected visually. The RIM101 signaling pathway was found to play an important role in this process.
FEMS YEAST RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Calla B. Shubin, Rini Mayangsari, Ariel D. Swett, Carol W. Greider
Summary: In budding yeast, Rif1 negatively regulates telomere length through a region with HEAT repeats that mediate telomere length regulation, separate from its proposed DNA binding function. Conserved amino acids from position 436 to 577 play a crucial role in telomere length regulation.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Lifang Yu, Mario Andrea Marchisio
Summary: This study presents an efficient tool to induce mRNA degradation in yeast using CRISPR-(d)Cas system, specifically (d)Cas12a. The study highlights the potential of V-A Cas proteins in yeast and demonstrates their applications in constructing Boolean logic gates.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Zachary W. Kockler, Josep M. Comeron, Anna Malkova
Summary: Based on the calculation of ALT frequencies and ultra-long sequencing of ALT products, this study demonstrates that both RAD51-dependent and RAD51-independent mechanisms are required for a unified ALT survivor pathway. The research provides insights into a potential unified ALT pathway that may operate in various organisms, including humans.
Article
Multidisciplinary Sciences
Zhen Zhou, Yuting Liu, Yushen Feng, Stephen Klepin, Lev S. Tsimring, Lorraine Pillus, Jeff Hasty, Nan Hao
Summary: Synthetic biology allows the design of gene networks for specific biological functions, but it is challenging to engineer the complex trait of longevity. By rewiring a naturally occurring toggle switch, we created a genetic clock that generates oscillations between nucleolar and mitochondrial aging processes, increasing cellular lifespan. These oscillations delay the commitment to aging caused by loss of chromatin silencing or heme depletion. Our study establishes a connection between gene network architecture and cellular longevity, potentially enabling the rational design of gene circuits to slow aging.
Article
Genetics & Heredity
Jose E. Perez-Ortin, Adriana Mena, Marina Barba-Aliaga, Abhyudai Singh, Sebastian Chavez, Jose Garcia-Martinez
Summary: In this study, the researchers investigated the synthesis mechanism of rRNA in yeast cells, and identified a volume-dependent RNA polymerase regulation mechanism to maintain rRNA homeostasis. The adjustment of transcription and translation rates according to the changing needs of cells is crucial for cell fitness and survival.
Article
Plant Sciences
Paige M. Henning, Joel S. Shore, Andrew G. McCubbin
Summary: A study has found that a member of the YUCCA gene family, YUC6, in heterostylous, self-incompatible Turnera species, determines the male mating type by regulating pollen size and physiological characteristics, without affecting the length dimorphism of filaments in anthers. This discovery reveals the biochemical basis and developmental window of male mating type.
Review
Genetics & Heredity
Bechara Zeinoun, Maria Teresa Teixeira, Aurelia Barascu
Summary: Telomeres are structures found at the ends of eukaryotic linear chromosomes that protect chromosomal tips and play roles in DNA repair. Telomeric long non-coding RNAs (LncRNAs), such as TERRA, have been discovered and shown to influence telomere function and length. TERRA interacts with telomerase and forms RNA:DNA hybrid structures, and its dysregulation has been associated with senescence and alternative lengthening of telomeres (ALT) pathways. This review focuses on the current understanding of TERRA in the budding yeast Saccharomyces cerevisiae, including its transcription, structure, expression, regulation, and functions.
Article
Multidisciplinary Sciences
Shihao Zhang, Xilan Yu, Yuan Zhang, Xiangyan Xue, Qi Yu, Zitong Zha, Madelaine Gogol, Jerry L. Workman, Shanshan Li
Summary: Telomeres, organized into heterochromatin, require maintenance of silent heterochromatin for chromosome stability. The study shows that Pyruvate kinase Pyk1 phosphorylates histone H3T11 and regulates gene expression through the SESAME complex. SESAME phosphorylates H3T11 at telomeres to maintain SIR complex occupancy and prevent autophagy-mediated Sir2 degradation, ultimately enhancing telomere silencing and protecting against compromised telomere silencing during aging.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Jan Padeken, Stephen Methot, Peter Zeller, Colin E. Delaney, Veronique Kalck, Susan M. Gasser
Summary: The study shows that the histone methyltransferase SET-25 in C. elegans can establish repressed chromatin domains, silencing novel insertions of transposons and tissue-specific genes during development. Two redundant pathways recruit SET-25 to its targets, with one pathway involving LIN-61 and MET-2, and the other pathway involving NRDE-3 and small RNAs, primarily targeting conserved transposons. The loss of these pathways results in the derepression of transposons in embryos, leading to increased embryonic lethality.
GENES & DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Romain Forey, Antoine Barthe, Mireille Tittel-Elmer, Maxime Wery, Marie-Benedicte Barrault, Cecile Ducrot, Andrew Seeber, Nils Krietenstein, Ugo Szachnowski, Magdalena Skrzypczak, Krzysztof Ginalski, Maga Rowicka, Jennifer A. Cobb, Oliver J. Rando, Julie Soutourina, Michel Werner, Karine Dubrana, Susan M. Gasser, Antonin Morillon, Philippe Pasero, Armelle Lengronne, Jerome Poli
Summary: Mre11-Rad50-Xrs2 (MRX) plays a new role in limiting transcription in budding yeast by physically interacting and colocalizing with the transcriptional co-regulator Mediator on chromatin. MRX restricts transcription of coding and noncoding DNA by tethering transcriptionally active loci to the nuclear pore complex (NPC), promoting gene-NPC interactions, contributing to chromosome folding, and controlling gene expression. These findings suggest a distinct role for MRX in transcription and chromosome organization apart from its known function in DNA repair.
Editorial Material
Biochemistry & Molecular Biology
Noriko Saitoh, Susan M. Gasser
Article
Biochemistry & Molecular Biology
Kiran Challa, Christoph D. Schmid, Saho Kitagawa, Anais Cheblal, Vytautas Iesmantavicius, Andrew Seeber, Assaf Amitai, Jan Seebacher, Michael H. Hauer, Kenji Shimada, Susan M. Gasser
Summary: In eukaryotic cells, checkpoint activation leads to degradation of core histones, resulting in reduced nucleosome occupancy. Extensive changes in chromatin-associated protein composition were observed after DNA damage, including loss of core histones, recruitment of ubiquitin ligases, and compromised DNA strand invasion kinetics during repair. This study provides a comprehensive overview of the genome-wide chromatin response to DNA damage.
Article
Biology
Kenji Shimada, Monika Tsai-Pflugfelder, Niloofar Davoodi Vijeh Motlagh, Neda Delgoshaie, Jeannette Fuchs, Heinz Gut, Susan M. Gasser
Summary: The study investigates mutations in the Pol31 segment of DNA polymerase delta, identifying substitutions that can restore deficiencies in pol32 Delta cells. These mutations not only affect DNA replication and repair processes but also impact recovery from pathways such as hydroxyurea, break-induced replication, and trans-lesion synthesis repair.
LIFE SCIENCE ALLIANCE
(2021)
Article
Biochemistry & Molecular Biology
Verena Hurst, Kiran Challa, Felix Jonas, Romain Forey, Ragna Sack, Jan Seebacher, Christoph D. Schmid, Naama Barkai, Kenji Shimada, Susan M. Gasser, Jerome Poli
Summary: In budding yeast, the Mec1 kinase plays a crucial role in evicting RNAPII and RNAPIII to facilitate replication fork progression. The non-phosphorylatable mec1-S1991A mutant hinders replication fork progression and compromises survival on hydroxyurea. Disrupting chromatin-bound RNAPII can alleviate the lethality in mec1-S1991A mutants.
Article
Cell Biology
Verena Hurst, Kiran Challa, Kenji Shimada, Susan M. Gasser
Summary: DNA damage induced by 405-nm laser light recruits proteins involved in base excision repair (BER), but perturbing actin or tubulin polymerization in human cells alters the dynamics of BER factors. Depolymerization of cytoplasmic actin may compromise BER efficiency in mammals due to increased levels of nuclear actin and tubulin, linking cytoskeletal integrity to BER.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Article
Cell Biology
Stephen P. Methot, Jan Padeken, Giovanna Brancati, Peter Zeller, Colin E. Delaney, Dimos Gaidatzis, Hubertus Kohler, Alexander van Oudenaarden, Helge Grosshans, Susan M. Gasser
Summary: The deposition of H3K9me2 and H3K9me3 can repress lineage-specific and germline genes in terminally differentiated Caenorhabditis elegans tissues by restricting the activity of specific transcription factors. Changes in H3K9me during development affect gene regulation and the maintenance of cellular functions.
NATURE CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Colin E. Delaney, Stephen P. Methot, Veronique Kala, Jan Seebacher, Daniel Hess, Susan M. Gasser, Jan Padeken
Summary: Genetic and genome-wide analysis of the SETDB1-like enzyme MET-2 in Caenorhabditis elegans reveals its role in promoting transcriptional silencing and fertility through both H3K9 methylation and focus formation. MET-2 has a noncatalytic function that contributes to gene repression. In normal development, MET-2 activity helps maintain fertility, while under heat stress, MET-2 foci disperse, resulting in increased acetylation and transcriptional derepression.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Review
Cell Biology
Jan Padeken, Stephen P. Methot, Susan M. Gasser
Summary: Heterochromatin is characterized by histone H3 Lys9 methylation, which ensures transcriptional silencing of repetitive elements and genes. The methyltransferases and "readers" of H3K9me2 or H3K9me3 are highly conserved and show redundancy. Loss or mistargeting of individual H3K9 methyltransferases can lead to impaired cell differentiation, loss of tissue identity, premature aging, and/or cancer. Recent studies in mammals have shed light on the roles of H3K9-specific histone methyltransferases in transcriptional homeostasis during tissue differentiation.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2022)
Correction
Biochemistry & Molecular Biology
Colin E. Delaney, Stephen P. Methot, Veronique Kalck, Jan Seebacher, Daniel Hess, Susan M. Gasser, Jan Padeken
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Editorial Material
Genetics & Heredity
Susan M. Gasser
Summary: In this interview, Professor Susan Gasser discusses her research on genome stability, epigenetic regulation, and chromatin organization, as well as her efforts in supporting women in research. She has made significant contributions to the field of chromatin structure and has been recognized with numerous awards and honors. She continues to actively promote the careers of women scientists in Europe and Japan.
Editorial Material
Biochemistry & Molecular Biology
Marta Rodriguez-Martinez, Jens Nielsen, Sam Dupont, Jessica Vamathevan, Beverley J. Glover, Lindsey C. Crosswell, Brendan Rouse, Ben F. Luisi, Chris Bowler, Susan M. Gasser, Detlev Arendt, Tobias J. Erb, Victor de Lorenzo, Edith Heard, Kiran Raosaheb Patil
Summary: Molecular biology has great potential in addressing climate change and biodiversity loss, but it is currently not well incorporated into strategies. We call for a community-wide action to bring molecular biology to the forefront of climate change solutions.
Review
Biochemistry & Molecular Biology
Susan M. Gasser, Francoise Stutz
Summary: The covalent linkage of Ubiquitin and SUMO to lysine residues plays important roles in DNA repair pathway choice and transcription regulation. SUMOylation mainly affects cellular processes by relocalizing modified proteins, particularly in response to DNA damage.
Editorial Material
Cell Biology
Susan M. M. Gasser
Summary: The compact state of chromatin induced by methylation of H3K9 on histone H3 is believed to be involved in heritable transcriptional repression. A recent study reveals that transient deposition of H3K9me3 helps stabilize stalled DNA replication forks, while its reversal allows for accurate fork restart.
NATURE CELL BIOLOGY
(2023)
