DNA Replication Group

Juan Méndez Group Leader
T +34 917328000 (Ext 3490)
jmendez@cnio.es

Research Scientists

Estrella Guarino
Susana Llanos
Sara Rodríguez

Post-Doctoral Fellows

Sergio Muñoz

Graduate Students

Miguel Curto
Carmen San Martín

The DNA Replication Group studies the process of genome duplication and its molecular alterations in cancer cells. In the past year, we have defined new genetic and regulatory elements of replication origins—the genomic regions that serve as starting sites for DNA synthesis. We have characterised a conserved DNA sequence motif and a new role for AURKA kinase in the regulation of origin activity. In parallel, we have investigated the molecular mechanisms by which primase-polymerase PRIMPOL facilitates DNA replication through damaged DNA. With this aim, we applied super-resolution microscopy techniques to the study of PRIMPOL, in collaboration with the group of Dr E. Rothenberg (New York University, NY, USA). Finally, we carried out a study with Dr E. Lecona (CBM Severo Ochoa, Madrid, Spain) showing how VCP/p97 ATPase regulates the activity of POLα/primase to regulate DNA replication and prevent the aberrant activation of checkpoint kinase ATR, which could jeopardise genomic stability.

Recent publications

Rodríguez-Acebes S, Martín-Rufo R, Gómez-Moya A, Churcher SB, Fernández-Llorente A, de la Vega-Barranco G, Perona A, Oroz P, Martín-Doncel E, Toledo LI, Méndez J & Lecona E (2025). DNA polymerase α/primase extraction from chromatin by VCP/p97 restricts ATR activation during unperturbed DNA replication. Nat Commun 16, 5706. CNIO Publication.
Muñoz S, Blanco-Romero E, González-Acosta D, Rodriguez-Acebes S, Megías D, Lopes M, Méndez J. (2024). RAD51 restricts DNA over-replication from re-activated origins. EMBO J 43, 1043-1064. CNIO Publication.
Muñoz S, Barroso S, Badra-Fajardo N, Marqueta-Gracia JJ, García-Rubio ML, Ubieto-Capella P, Méndez J, Aguilera A. (2024). SIN3A histone deacetylase action counteracts MUS81 to promote stalled fork stability. Cell Reports 43, 113778. CNIO Publication.
Ubieto-Capella P, Ximénez-Embún P, Giménez-Llorente D, Losada A, Muñoz J, Méndez J. (2024). A rewiring of DNA replication mediated by MRE11 exonuclease underlies primed-to-naive cell de-differentiation. Cell Reports 43, 114024. CNIO Publication.
Llanos S, Di Geronimo B, Casajús E, Blanco-Romero E, Fernández-Leiro R, Méndez J. (2024). Interference of small compounds and Mg2+ with dsRNA-binding fluorophores compromises the identification of SARS-CoV-2 RdRp inhibitors. Sci Rep 14, 28250. CNIO Publication.
Fütterer A, Rodriguez-Acebes S, Méndez J, Gutiérrez J, Martínez-A C. (2024). PARP1, DIDO3, and DHX9 Proteins Mutually Interact in Mouse Fibroblasts, with Effects on DNA Replication Dynamics, Senescence, and Oncogenic Transformation. Cells 13, 159. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication. Open Access
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. CNIO Publication.
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. CNIO Publication.
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. CNIO Publication. 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. CNIO Publication.