Grupo de Replicación de ADN

Juan Méndez Jefe de Grupo
T +34 917328000 (Ext 3490)
jmendez@cnio.es

Investigadores Científicos

Estrella Guarino
Susana Llanos
Sara Rodríguez

Becarios Post-doctorales

Sergio Muñoz

Becarios Pre-Doctorales

Elena Blanco
Roberto Masdemont
Sergi Roig
Patricia Ubieto

Despite the biochemical complexity of the DNA replication process, the molecular machinery that duplicates our genome displays a remarkable capacity to adapt to different cell types, each one with its own transcriptional programme and specific patterns of chromatin organisation. In addition, the replisome proteins react to endogenous and exogenous factors that induce replicative stress (RS) and may cause DNA breaks, recombination events, and genomic instability. Our Group studies the mechanisms that confer operational flexibility to the replicative process, combining molecular and cellular approaches in human and mouse cells. In 2022, we completed two studies describing the cellular responses to specific situations of stress, which involve the regulation of origin activity and the control over replication fork progression. We also continued to study the dynamics of DNA replication and the impact of RS in other cellular contexts, including the acquisition of metastatic capacity by tumour cells.

Publicaciones

Debaugnies M, Rodríguez-Acebes S, Blondeau J, Parent MA, Zocco M, Song Y, de Maertelaer V, Moers V, Latil M, Dubois C, Coulonval K, Impens F, Van Haver D, Dufour S, Uemura A, Sotiropoulou PA, Méndez J, Blanpain C. (2023). RHOJ controls EMT-associated resistance to chemotherapy. Nature 616, 168-175. Publicación CNIO.
Fuertes T, Álvarez-Corrales E, Gómez-Escolar C, Ubieto-Capella P, Serrano-Navarro Á, de Molina A, Méndez J, Ramiro AR, de Yébenes VG (2023). miR-28-based combination therapy impairs aggressive B cell lymphoma growth by rewiring DNA replication. Cell Death Dis 14, 687. Publicación CNIO.
Jacobs K, Doerdelmann C, Krietsch J, González-Acosta D, Mathis N, Kushinsky S, Guarino E, Gómez-Escolar C, Martinez D, Schmid JA, Leary PJ, Freire R, Ramiro AR, Eischen CM, Mendez J, Lopes M (2022). Stress-triggered hematopoietic stem cell proliferation relies on PrimPol-mediated repriming. Mol Cell 38, 4176-4188. Publicación CNIO.
Jodkowska K, Pancaldi V, Rigau M, Almeida R, Fernández-Justel JM, Graña-Castro O, Rodríguez-Acebes S, Rubio-Camarillo M, Carrillo-de Santa Pau E, Pisano D, Al-Shahrour F, Valencia A, Gómez M, Méndez J. (2022). 3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells. Nucleic Acids Res 50, 12149-12165. Publicación CNIO.
Franca MM, Condezo YB, Elzaiat M, Felipe-Medina N, Sánchez-Sáez F, Muñoz S, Sainz-Urruela R, Martín-Hervás MR, García-Valiente R, Sánchez-Martín MA, Astudillo A, Mendez J, Llano E, Veitia RA, Mendonca BB, Pendás AM (2022). A truncating variant of RAD51B associated with primary ovarian insufficiency provides insights into its meiotic and somatic functions. Cell Death Differ 29, 2347-2361. Publicación CNIO.
Ulsamer A, Martínez-Limón A, Bader S, Rodríguez-Acebes S, Freire R, Méndez J, de Nadal E, Posas F (2022). Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage. Cell Reports 40, 111375. Publicación CNIO.
Calvo PA, Martínez-Jiménez MI, Díaz M, Stojkovic G, Kasho K, Guerra S, Wanrooij S, Méndez J, Blanco L. (2021). Motif WFYY of human PrimPol is crucial to stabilize the incoming 3′-nucleotide during replication fork restart. Nucleic Acids Res 49, 8199-8213. Publicación CNIO. Open Access
González-Acosta D, Blanco-Romero E, Ubieto-Capella P, Mutreja K, Míguez S, Llanos S, García F, Muñoz J, Blanco L, Lopes M, Méndez J (2021). PrimPol-mediated repriming facilitates replication traverse of DNA interstrand crosslinks. EMBO J 40, e106355. Publicación CNIO.
Quinet A, Tirman S, Jackson J, Švikovic S, Lemaçon D, Carvajal-Maldonado D, González-Acosta D, Vessoni AT, Cybulla E, Wood M, Tavis S, Batista LFZ, Méndez J, Sale JE, Vindigni A. (2020). PRIMPOL-Mediated Adaptive Response Suppresses Replication Fork Reversal in BRCA-Deficient Cells.. Mol Cell 77, 461-474. Publicación CNIO.
Piberger AL, Bowry A, Kelly RDW, Walker AK, González-Acosta D, Bailey LJ, Doherty AJ, Méndez J, Morris JR, Bryant HE, Petermann E (2020). PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts. Nat Commun 11, 5863. Publicación CNIO. Open Access
Morales C, Ruiz-Torres M, Rodríguez-Acebes S, Lafarga V, Rodríguez-Corsino M, Megías D, Cisneros DA, Peters JM, Méndez J, Losada A (2020). PDS5 proteins are required for proper cohesin dynamics and participate in replication fork protection. J Biol Chem 295, 146-157. Publicación CNIO. Open Access
Lafarga V, Sung H-M, Haneke K, Roessig L, Pauleau A-L, Bruer M, Rodríguez-Acebes S, López-Contreras A, Gruss OJ, Erhardt S, Méndez J, Fernández-Capetillo O, Stoecklin G (2019). TIAR controls mitotic entry, maintains genome stability and retains CDK1 in checkpoint bodies.. EMBO Rep 20, pii: e46224. Publicación CNIO.
Triana-Martínez F, Picallos-Rabina P, Da Silva-Álvarez S, Pietrocola F, Llanos S, Rodilla V, Soprano E, Pedrosa P, Ferreirós A, Barradas M, Hernández-González F, Lalinde M, Prats N, Bernadó C, González P, Gómez M, Ikonomopoulou MP, Fernández-Marcos PJ, García-Caballero T, Del Pino P, Arribas J, Vidal A, González-Barcia M, Serrano M, Loza MI, Domínguez E, Collado M (2019). Identification and characterization of Cardiac Glycosides as senolytic compounds.. Nat Commun 10, 4731. Publicación CNIO. Open Access
Lafarga V, Sung HM, Haneke K, Roessig L, Pauleau AL, Bruer M, Rodriguez-Acebes S, Lopez-Contreras AJ, Gruss OJ, Erhardt S, Mendez J, Fernandez-Capetillo O, Stoecklin G (2019). TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress. EMBO Rep 20, e46224. Publicación CNIO.
Llanos S, Megias D, Blanco-Aparicio C, Hernández-Encinas E, Rovira M, Pietrocola F, Serrano M (2019). Lysosomal trapping of palbociclib and its functional implications. Oncogene 38, 3886-3902. Publicación CNIO.
Díaz-Talavera A, Calvo PA, González-Acosta D, Díaz M, Sastre-Moreno G, Blanco-Franco L, Guerra S, Martínez-Jiménez MI, Méndez J, Blanco L (2019). A cancer-associated point mutation disables the steric gate of human PrimPol. Sci Rep 9, 1121. Publicación CNIO. Open Access
Jodkowska K, Pancaldi V, Almeida R, Rigau M, Graña-Castro O, Fernández-Justel JM, Rodríguez-Acebes S, Rubio-Camarillo M, Carrillo-de Santa Pau E, Pisano D, Al-Sharhrour F, Valencia A, Gómez M, Méndez J (2019). Three-dimensional connectivity and chromatin environment mediate the activation efficiency of mammalian DNA replication origins.. bioRxiv (in press). Publicación CNIO.
Pérez-Olivares M, Trento A, Rodriguez-Acebes S, González-Acosta D, Fernández-Antorán D, Román-García S, Martinez D, López-Briones T, Torroja C, Carrasco YR, Méndez J, Moreno de Alborán I (2018). Functional interplay between c-Myc and Max in B lymphocyte differentiation. EMBO Rep 19, e45770. Publicación CNIO.
Rodriguez-Acebes S, Mourón S, Méndez J (2018). Uncoupling fork speed and origin activity to identify the primary cause of replicative stress phenotypes. J Biol Chem 293, 12855-12861. Publicación CNIO.