Investigadores
- Susana Llanos
- Sara Rodríguez
Becarios Pre-Doctorales
- Elena Blanco
- Daniel González
- Patricia Ubieto
Técnicos de Laboratorio
- Sara San José
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.
Publicaciones
- (2019). TIAR controls mitotic entry, maintains genome stability and retains CDK1 in checkpoint bodies.. EMBO Rep 20, pii: e46224-.
- (2019). Lysosomal trapping of palbociclib and its functional implications. Oncogene (in press).
- (2019). TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress. EMBO Rep (in press).
- (2019). A cancer-associated point mutation disables the steric gate of human PrimPol. Sci Rep 9, 1121-.
- (2018). Functional interplay between c-Myc and Max in B lymphocyte differentiation. EMBO Rep 19, e45770-.
- (2018). Uncoupling fork speed and origin activity to identify the primary cause of replicative stress phenotypes. J Biol Chem 293, 12855-12861.
- (2017). In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias.. Cell Reports 19, 928-938.
- (2017). Shortage of dNTPs underlies altered replication dynamics and DNA breakage in the absence of the APC/C cofactor Cdh1.. Oncogene 36, 5808-5818.
- (2017). DNA replication stress: from molecular mechanisms to human disease.. Chromosoma 126, 1-15.
- (2016). USP7 is a SUMO deubiquitinase essential for DNA replication.. Nat Struct Mol Biol 23, 270-277.
- (2016). POLD3 Is Haploinsufficient for DNA Replication in Mice.. Mol Cell 63, 877-883.
- (2016). A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells.. Nat Communications 7, 10660-.
- (2016). USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.. Mol Oncol 10, 1196-1206.
- (2016). DNA replication stress: from molecular mechanisms to human disease.. Chromosoma (in press).
- (2016). Molecular architecture of the recombinant human MCM2-7 helicase in complex with nucleotides and DNA.. Cell Cycle 15, 2431-2440.
- (2015). NSMCE2 suppresses cancer and aging in mice independently of its SUMO ligase activity.. EMBO J 34, 2604-2619.
- (2015). Functional reprogramming of polyploidization in megakaryocytes.. Dev Cell 32, 155-167.
- (2015). Deregulated expression of Cdc6 in the skin facilitates papilloma formation and affects the hair growth cycle.. Cell Cycle 14, 3897-3907.
- (2015). Replication stress caused by low MCM expression limits fetal erythropoiesis and hematopoietic stem cell functionality.. Nat Communications 6, 8548-.
- (2014). Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells.. Nature 512, 198-202.
- (2013). A proteomic characterization of factors enriched at nascent DNA molecules.. Cell Reports 3, 1-12.
- (2013). PrimPol, an archaic primase/polymerase operating in human cells.. Mol Cell 52, 541-553.
- (2013). Repriming of DNA synthesis at stalled replication forks by human PrimPol.. Nat Struct Mol Biol 20, 1383-1389.