Genomic instability and cancer
PRINCIPAL INVESTIGATOR
Félix M. Machín Concepción, PhD
Contracted Investigator SCS/FIISC, HUNSC Research Unit |
PHD STUDENTS AND TRAINEES:
- Emiliano Matos Perdomo (PhD student, ULL)
- Laura Anaissi Afonso (PhD student, ULL. The Canary Islands Agency of Research, Innovation and Information Sciences, ACIISI)
- Jessel Ayra Plasencia (PhD student, ULL)
- Silvia Santana Sosa (PhD student, ULL. The Canary Islands Agency of Research, Innovation and Information Sciences, ACIISI)
TECHNICAL AND ADMINISTRATIVE STAFF:
- Isabel Lorenzo Castrillejo (Laboratory technician, FP2, HUNSC)
RESEARCH LINES:
Genetic instability hinders the ability of cells to pass an accurate copy of their genetic information to their progeny, which leads to cancer and other degenerative diseases. Genetic instability underlies the genetic diversity present in tumours, which accounts for malignancy and resistance to treatment. DNA damage and chromosome mis-segregation during cell division are the most common causes of genetic instability, which are paradoxically also the mechanisms of action of most anti-tumour drugs used to combat cancer cells. Our research focuses on understanding these phenomena and their contribution to the complexity of cancer biology. For these studies we use model organisms like Saccharomyces cerevisiae and occasionally, cell lines like HeLa.
We are also interested in chemical compounds affecting DNA, microtubules, mitochondria, plasma membrane, topoisomerases, protein aggregation, the apoptotic pathway, etc., and their potential use as anti-tumour, antibiotic, anti-fungal and anti-parasitic therapies.
FUNDED PROJECTS:
- Characterisation of the signalling and repair of telophase DNA breaks and anaphase bridges. (BFU2017-83954-R – “Caracterización de la señalización y reparación de la rotura del ADN en telofase y en los puentes de anafase”). PI: Félix Machín. Ministry of Economy and Competitiveness, MINECO (018-2021, 170,610 €)
- Screening for natural and synthetic compounds in chemical libraries from The Canary Islands with bio-pharmacological effects combating neurodegenerative disorders (“Identificación de compuestos naturales y sintéticos presentes en las quimiotecas canarias con potencial biofarmacológico contra enfermedades neurodegenerativas”). PI: Félix Machín. The Canary Islands Agency for Research, Innovation and Information Sciences, ACIISI (2018-2020, 70,000 €)
- Screening for anti-apoptotic activities against degenerative diseases in collections of active substances of biomedical interest (“Rastreo de actividades anti-apoptóticas contra enfermedades degenerativas entre colecciones de principios activos de interés biomédico “: PIFIIS19/04). PI: Félix Machín. The Canary Islands Health Research Institute Foundation, FIISC (2020-2022; 28,162.40 €)
PUBLICATIONS 2019:
- Ayra-Plasencia J, Machín F. DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci. Nature Communications. 2019 Jun 28;10(1):2862. doi: 10.1038/s41467-019-10742-8
- Matos-Perdomo E, Machín F. Nucleolar and Ribosomal DNA Structure under Stress: Yeast Lessons for Aging and Cancer. Cells. 2019 Jul 26;8(8). pii: E779. doi: 10.3390/cells8080779
- Ayra-Plasencia J, Machín F. Yeast cells can partially revert chromosome segregation to repair late DNA double-strand breaks through homologous recombination. Mol Cell Oncol. 2019 Aug 6;6(5):e1648027. doi: 10.1080/23723556.2019.1648027
- Ramos-Pérez C, Dominska M, Anaissi-Afonso L, Cazorla-Rivero S, Quevedo O, Lorenzo-Castrillejo I, Petes TD, Machín F. Cytological and genetic consequences for the progeny of a mitotic catastrophe provoked by Topoisomerase II deficiency. Aging (Albany NY). 2019 Dec 8;11(23):11686-11721. doi: 10.18632/aging.102573
OTHER SELECTED PUBLICATIONS FROM THE LAST 10 YEARS:
- Anaissi-Afonso L, Oramas-Royo S, Ayra-Plasencia J, Martín-Rodríguez P, García-Luis J, Lorenzo-Castrillejo I, Fernández-Pérez L, Estévez-Braun A, Machín F. Lawsone, Juglone, and β-Lapachone Derivatives with Enhanced Mitochondrial-Based Toxicity. ACS Chem Biol. 2018 Aug 17;13(8):1950-1957. doi: 10.1021/acschembio.8b00306
- Quevedo O, Ramos-Perez C, Petes TD, Machín F. The transient inactivation of the master cell cycle phosphatase Cdc14 causes genomic inestability in diploid cells of saccharamyces cerevisiae. Genetics. 2015 Jul;200(3):755-69. doi:10.1534/genetics.115.177626
- García-Luis J, Machín F. Mus81-Mms4 and Yen1 resolve a novel anaphase bridge formed by noncanonical Holliday junctions. Nat Commun. 2014 Dec 3;5:5652. doi:10.1038/ncomms6652
- Garcia-Luis J, Clemente-Blanco A, Aragon L, Machín F. Cdc14 targets the Holliday junction solvase Yen1 to the nucleus in early anaphase. Cell Cycle. 2014;13(9):1392-9. doi: 10.4161/cc.28370
- Quevedo O, Garcia-Luis J, Matos-Perdomo E, Aragon L, Machín F. Non-disjunction of a single chromosome leads to breakage and activation of DNA damage checkpoint in G2. PLoS Genet. 2012;8(2):e1002509. doi:10.1371/journal.pgen.1002509