A5018003481- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- DNA Repair Mechanisms
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Genomic variations and chromosomal abnormalities
- CRISPR and Genetic Engineering
- DNA and Nucleic Acid Chemistry
- Telomeres, Telomerase, and Senescence
- RNA and protein synthesis mechanisms
- Cellular Mechanics and Interactions
- FOXO transcription factor regulation
- Cancer-related gene regulation
- BRCA gene mutations in cancer
- RNA regulation and disease
University of Edinburgh
2018-2025
Wellcome Centre for Cell Biology
2018-2024
Institute of Cell Biology
2024
Instituto Nacional de Cancerología
2013-2022
Universidad Nacional Autónoma de México
2012-2022
Harvard University
2020
Boston University
2020
An additional cell cycle checkpoint Cell division is controlled by checkpoints that regulate the temporal order of phases, including G 1 /S, 2 /M, and metaphase/anaphase transitions. Yet there are no known control mechanisms for a fourth fundamental transition—the S/G transition. Saldivar et al. report switchlike mechanism regulates The kinase ATR senses ongoing DNA replication in S phase represses mitotic transcriptional network, ensuring completed before mitosis. Science , this issue p. 806
Abstract During mitosis, interphase chromatin is rapidly converted into rod-shaped mitotic chromosomes. Using Hi-C, imaging, proteomics and polymer modeling, we determine how the activity interplay between loop-extruding SMC motors accomplishes this dramatic transition. Our work reveals rules of engagement for complexes that are critical allowing cells to refold We find condensin disassembles loop organization by evicting or displacing extrusive cohesin. In contrast, bypasses cohesive...
We used Hi-C, imaging, proteomics, and polymer modeling to define rules of engagement for SMC (structural maintenance chromosomes) complexes as cells refold interphase chromatin into rod-shaped mitotic chromosomes. First, condensin disassembles loop organization by evicting or displacing extrusive cohesin. Second, bypasses cohesive cohesins, thereby maintaining sister chromatid cohesion sisters separate. Studies chromosomes formed cohesin, II, I alone in combination lead refined models...
Chromosome compaction is a key feature of mitosis and critical for accurate chromosome segregation. However, precise quantitative analysis geometry during mitotic progression lacking. Here, we use volume electron microscopy to map, with nanometer precision, chromosomes from prometaphase through telophase in human RPE1 cells. During prometaphase, acquire smoother surface, their arms shorten, the primary centromeric constriction formed. The chromatin progressively compacted, ultimately...
Abstract Background In cancer cells, transcriptional gene silencing has been associated with genetic and epigenetic defects. The disruption of DNA methylation patterns covalent histone marks development. Until recently, microRNA (miRNA) was not well understood. particular, miR-125b1 suggested to be an miRNA tumor suppressor activity, it shown deregulated in various human cancers. the present study, we evaluated at CpG island proximal transcription start site cell lines as normal tissues...
Downregulation of miR-125b-1 is associated with poor prognosis in breast cancer patients. In this work we investigated the effect histone modifications on regulation gene promoter.We evaluated enrichment two involved repression, H3K9me3 and H3K27me3, promoter cell lines, MCF7 (luminal A subtype) MDA-MB-231 (triple-negative subtype), compared to non-transformed line MCF10A. H3K27me3 were enriched cells, respectively. Next, used an EZH2 inhibitor examine reactivation cells transcriptional...
Most eukaryotic centromeres are located within heterochromatic regions. Paradoxically, heterochromatin can also antagonize de novo centromere formation, and some lack it altogether. In order to investigate the importance of at centromeres, we used epigenetic engineering a synthetic alphoidtetO human artificial chromosome (HAC), which chimeric proteins be targeted. By tethering JMJD2D demethylase (also known as KDM4D), removed mark H3K9me3 (histone 3 lysine 9 trimethylation) specifically from...
Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of by 80% 40%. The most common pathogenic variants (PVs) causing HBOC occur in BRCA1 gene, with more than 3850 reported mutations gene sequence. prevalence specific PVs has increased across populations due to effect founder mutations. Therefore, when mutation identified, it becomes key improving characterization effective screening protocols. only described Mexican population deletion exons 9...
Abstract Spindle poisons activate the spindle assembly checkpoint and prevent mitotic exit until cells die or override arrest. Several studies have focused on poison-mediated cell death, but less is known about consequences in that survive a During mitosis, proteins such as CYCLIN B, SECURIN, BUB1 SURVIVIN are degraded order to allow exit, these maintained at low levels next interphase. In contrast, from prolonged mitosis depends only degradation of B; it not whether other decrease remain...
e22151 Background: Genetic and epigenetic alterations may promote the initiation or development of cancer. Global DNA hypomethylation local hypermethylation have been observed, particularly in cell cycle control-associated genes, such as tumor suppressor genes like CTCF. The dissociation CTCF is associated with several promoters; its paralogue gene (BORIS) normally expressed testicular tissue during spermatogenesis. BORIS over-expression has identified multiple neoplasms melanoma,...
The long noncoding RNA (lncRNA) telomeric repeat-containing (TERRA) has been associated with homeostasis, telomerase recruitment, and the process of chromosome healing; nevertheless, impact this association not investigated during carcinogenic process. Determining whether changes in TERRA expression are a cause or consequence cell transformation is complex task because studies usually carried out using either cancerous cells tumor samples. To determine role lncRNA cellular aging healing, we...
Abstract miR-125b-1 downregulates targets as ERBB2, BAK1 and ETS1. These are involved in cell proliferation, apoptosis migration, respectively. Previous studies on tumor cells reveal that downregulation of is associated with poor prognosis breast cancer patients. DNA methylation the promoter can repress its expression, addition, this embedded an intermediate CpG island thus, histone modifications could also affect transcription. Repression by has been well characterized, but there no...
Background In cancer cells, transcriptional gene silencing has been associated with genetic and epigenetic defects. The disruption of DNA methylation patterns covalent histone marks development. non-neoplastic cells the multifunctional CCCTC-binding factor (CTCF) can serve as a barrier against spread repressive into promoter regions tumor suppressor genes such BRCA1, Rb, p16 p53. absence CTCF related its silencing. Until recently, microRNA (miRNA) was not well understood. particular, miR-...
ABSTRACT First Person is a series of interviews with the first authors selection papers published in Journal Cell Science, helping early-career researchers promote themselves alongside their papers. Nuno Martins, Fernanda Cisneros-Soberani and Elisa Pesenti are co-first on ‘H3K9me3 maintenance human artificial chromosome required for segregation but not centromere epigenetic memory’, JCS. conducted research described this article while PhD student William C. Earnshaw's lab at Wellcome Trust...