Biology subjects

Mendoza, M.

Publications and source records attributed to Mendoza, M..

5 recordsLinked to original sources

bioRxiv2018

Budding yeast complete DNA replication after chromosome segregation begins

To faithfully transmit genetic information, cells must replicate their entire genome before division. This is thought to be ensured by the temporal separation of replication and chromosome segregation. Here we show that in a substantial fraction of unperturbed yeast cells, DNA replication finishes during anaphase, late in mitosis. High cyclin-Cdk activity inhibits replication in metaphase, and the decrease in cyclin-Cdk activity during mitotic exit allows DNA replication to finish at difficult-to-replicate regions. Replication during late mitosis correlates with elevated mutation rates, including copy number variation. Thus, yeast cells temporally overlap replication and chromosome segregation during normal growth, possibly allowing cells to maximize population-level growth rate while simultaneously exploring greater genetic space.\n\nOne Sentence SummaryCompletion of DNA replication is coupled to downregulation of Cyclin-Dependent Kinase during mitotic exit.

cell biology↗

bioRxiv2017

The spatial position of budding yeast chromosomes affects gene expression

The three-dimensional organization of chromosomes can influence transcription. However, the frequency and magnitude of these effects remains debated. To determine how changes in chromosome positioning affect transcription across thousands of genes with minimal perturbation, we characterized nuclear organization and global gene expression in budding yeast containing chromosome fusions. We used computational modelling and single cell imaging to determine chromosome position and integrated these data with genome-wide transcriptional profiles from RNA sequencing. We find that chromosome fusions dramatically alter 3D nuclear organization without leading to strong genome-wide changes in transcription. However, we observe a mild but significant and reproducible increase in expression of genes near fusion sites. Modeling suggests that this is due to both disruption of telomere-associated silencing and the displacement of genes relative to the nuclear periphery. A 10% decrease in the predicted time a gene spends near the nuclear periphery is associated with a 10% increase in expression. These data suggest that basal transcriptional activity is sensitive to radial changes on gene position, and provide insight into the functional relevance of budding yeast chromosome-level three-dimensional organization in gene expression.

cell biology↗

bioRxiv2017

Is the LAN effect in morphosyntactic processing an ERP artifact?

The left anterior negativity (LAN) is an ERP component that has been often associated with morphosyntactic processing, but recent reports have questioned whether the LAN effect, in fact, exists. The present project examined whether the LAN effect, observed in the grand average response to local agreement violations, is the result of the overlap between two different ERP effects (N400, P600) at the level of subjects (n=80), items (n=120), or trials (n=6160). By-subject, by-item, and by-trial analyses of the ERP effect between 300 and 500 ms showed a LAN for 55% of the participants, 46% of the items, and 49% of the trials. Many examples of the biphasic LAN-P600 response were observed. Mixed-linear models showed that the LAN effect size was not reduced after accounting for subject variability. The present results suggest that there are cases where the grand average LAN effect represents the brain responses of individual participants, items, and trials.

neuroscience↗

bioRxiv2017

Cell-specific modulation of nuclear pore complexes controls cell cycle entry during asymmetric division

The acquisition of cellular identity is coupled to changes in the nuclear periphery and nuclear pore complexes (NPCs). Whether and how these changes determine cell fate remains unclear. We have uncovered a mechanism regulating NPC acetylation to direct cell fate after asymmetric division in budding yeast. The lysine deacetylase Hos3 associates specifically with daughter cell NPCs during mitosis to delay cell cycle entry (Start). Hos3-dependent deacetylation of nuclear basket and central channel nucleoporins establishes daughter cell-specific nuclear accumulation of the transcriptional repressor Whi5 during anaphase and perinuclear silencing of the CLN2 gene in the following G1 phase. Hos3-dependent coordination of both events restrains Start in daughter but not in mother cells. We propose that deacetylation modulates transport-dependent and - independent functions of NPCs, leading to differential cell cycle progression in mother and daughter cells. Similar mechanisms might regulate NPC functions in specific cell types and/or cell cycle stages in multicellular organisms.

cell biology↗

bioRxiv2017

Distinct roles of the polarity factors Boi1 and Boi2 in the control of exocytosis and abscission in budding yeast

Boi1 and Boi2 (Boi1/2) are budding yeast plasma membrane proteins that function in polarized growth, and in cytokinesis inhibition in response to chromosome bridges via the NoCut abscission checkpoint. How Boi1/2 act in these two distinct processes is not understood. We demonstrate that Boi1/2 are required for a late step in the fusion of secretory vesicles with the plasma membrane of the growing bud. Cells lacking Boi1/2 accumulate secretory vesicles and are defective in bud growth. In contrast, Boi2 is specifically required for abscission inhibition in cells with chromatin bridges. The SH3 domain of Boi2, which is dispensable for bud growth and targets Boi2 to the site of abscission, is essential for abscission inhibition. Gain of function of the exocyst, a conserved protein complex involved in tethering of exocytic vesicles to the plasma membrane, rescued secretion and bud growth defects in boi mutant cells, and abrogated NoCut checkpoint function. Thus, Boi2 functions redundantly with Boi1 to promote the fusion of secretory vesicles with the plasma membrane at sites of polarized growth, and acts as an abscission inhibitor during cytokinesis in response to chromatin bridges.

cell biology↗