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

Up to two thirds of the total mutations detected in tumours are caused by inaccurate DNA replication. Our laboratory studies the process of DNA replication using a combination of biochemistry, cell biology and mouse genetics. Our current interests include: (1) the genetic and epigenetic elements that define replication origins; (2) the cellular responses to replicative stress (RS) caused by endogenous elements (e.g. natural decay of DNA; collisions between replication and transcription proteins) or exogenous factors such as UV radiation or DNA-damaging chemical agents. One of the responses to RS is the activation of ‘dormant’ origins, whose regulation remains poorly understood; (3) the mechanisms that limit DNA replication to only one round in each cell cycle, and the physiological consequences of their malfunction; and (4) the role of PrimPol, a recently characterised enzyme with primase and polymerase activities, in the ‘tolerance’ mechanisms that enable replication through damaged DNA.

Publications

• TIAR controls mitotic entry, maintains genome stability and retains CDK1 in checkpoint bodies.(2019)
  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
  EMBO Rep 20, pii: e46224-.
• Functional interplay between c-Myc and Max in B lymphocyte differentiation.(2018)
  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.
  EMBO Rep 19, e45770-.
• Uncoupling fork speed and origin activity to identify the primary cause of replicative stress phenotypes.(2018)
  Rodriguez-Acebes S, Mourón S, Méndez J.
  J Biol Chem 293, 12855-12861.
• In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias.(2017)
  Muñoz S, Búa S, Rodríguez-Acebes S, Megías D, Ortega S, de Martino A, Méndez J
  Cell Reports 19, 928-938.
• Shortage of dNTPs underlies altered replication dynamics and DNA breakage in the absence of the APC/C cofactor Cdh1.(2017)
  Garzón J, Rodríguez R, Kong Z, Chabes A, Rodríguez-Acebes S, Méndez J, Moreno S, García-Higuera I.
  Oncogene 36, 5808-5818.
• DNA replication stress: from molecular mechanisms to human disease.(2017)
  Muñoz S, Méndez J
  Chromosoma 126, 1-15.
• USP7 is a SUMO deubiquitinase essential for DNA replication.(2016)
  Lecona E, Rodriguez-Acebes S, Specks J, Lopez-Contreras AJ, Ruppen I, Murga M, Muñoz J, Mendez J, Fernandez-Capetillo O
  Nat Struct Mol Biol 23, 270-277.
• POLD3 Is Haploinsufficient for DNA Replication in Mice.(2016)
  Murga M, Lecona E, Kamileri I, Díaz M, Lugli N, Sotiriou SK, Anton ME, Méndez J, Halazonetis TD, Fernandez-Capetillo O
  Mol Cell 63, 877-883.
• A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells.(2016)
  Ahuja AK, Jodkowska K, Teloni F, Bizard AH, Zellweger R, Herrador R, Ortega S, Hickson ID, Altmeyer M, Mendez J, Lopes M
  Nat Communications 7, 10660-.
• USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.(2016)
  Hernández-Pérez S, Cabrera E, Amoedo H, Rodríguez-Acebes S, Koundrioukoff S, Debatisse M, Méndez J, Freire R
  Mol Oncol 10, 1196-1206.
• DNA replication stress: from molecular mechanisms to human disease.(2016)
  Muñoz S, Méndez J
  Chromosoma (in press).
• Molecular architecture of the recombinant human MCM2-7 helicase in complex with nucleotides and DNA.(2016)
  Boskovic J, Bragado-Nilsson E, Saligram Prabhakar B, Yefimenko I, Martínez-Gago J, Muñoz S, Méndez J, Montoya G
  Cell Cycle 15, 2431-2440.
• NSMCE2 suppresses cancer and aging in mice independently of its SUMO ligase activity.(2015)
  Jacome A, Gutierrez-Martinez P, Schiavoni F, Tenaglia E, Martinez P, Rodríguez-Acebes S, Lecona E, Murga M, Méndez J, Blasco MA, Fernandez-Capetillo O
  EMBO J 34, 2604-2619.
• Functional reprogramming of polyploidization in megakaryocytes.(2015)
  Trakala M, Rodríguez-Acebes S, Maroto M, Symonds CE, Santamaría D, Ortega S, Barbacid M, Méndez J, Malumbres M.
  Dev Cell 32, 155-167.
• Deregulated expression of Cdc6 in the skin facilitates papilloma formation and affects the hair growth cycle.(2015)
  Búa S, Sotiropoulou P, Sgarlata C, Borlado, LR, Eguren M, Domínguez O, Ortega S, Malumbres M, Blanpain C, Méndez J
  Cell Cycle 14, 3897-3907.
• Replication stress caused by low MCM expression limits fetal erythropoiesis and hematopoietic stem cell functionality.(2015)
  Alvarez S, Díaz M, Flach J, Rodriguez-Acebes S, López-Contreras AJ, Martínez D, Cañamero M, Fernández-Capetillo O, Isern J, Passegué E, Méndez J
  Nat Communications 6, 8548-.
• Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells.(2014)
  Flach J, Bakker ST, Mohrin M, Conroy PC, Pietras EM, Reynaud D, Alvarez S, Diolaiti ME, Ugarte F, Forsberg EC, Le Beau MM, Stohr BA, Méndez J, Morrison C, Passegué E
  Nature 512, 198-202.
• A proteomic characterization of factors enriched at nascent DNA molecules.(2013)
  López-Contreras AJ, Ruppen I, Nieto-Soler M, Murga M, Rodriguez- Acebes S, Remeseiro S, Rodrigo-Perez S, Rojas AM, Mendez J, Muñoz J, Fernandez-Capetillo O
  Cell Reports 3, 1-12.
• PrimPol, an archaic primase/polymerase operating in human cells.(2013)
  García-Gómez S, Reyes A, Martínez-Jiménez MI, Chocrón ES, Mourón S, Terrados G, Powell C, Salido E, Méndez J, Holt IJ, Blanco L
  Mol Cell 52, 541-553.
• Repriming of DNA synthesis at stalled replication forks by human PrimPol.(2013)
  Mourón S, Rodriguez-Acebes S, Martínez-Jiménez MI, García-Gómez S, Chocrón S, Blanco L, Méndez J
  Nat Struct Mol Biol 20, 1383-1389.