Investigadores
- Susana Llanos
- Sara Rodríguez
Becarios Pre-Doctorales
- Elena Blanco
- Daniel González
- Patricia Ubieto
Técnicos de Laboratorio
- Sara San José
Recent epidemiology studies indicate that up to two thirds of the mutations found in tumours are the consequence of inaccurate DNA replication; the rest are inherited or caused by environmental factors. We study the process of DNA replication and its regulatory pathways, with a particular interest in the phenomenon of replicative stress (RS) caused by the temporal stalling or inhibition of the protein machinery responsible for DNA synthesis. In 2018, we focused on the following areas: (1) the activation of ‘dormant’ replication origins in response to RS; (2) the molecular connection between the speed of replication forks and the frequency of origin activation, the two main parameters affected by RS; and (3) the function of PrimPol primase in ‘replicative tolerance’, i.e. the duplication of chemically damaged DNA molecules in order to facilitate their subsequent repair. We have also applied single-molecule methods to analyse the impact of RS in several biological processes.
Publicaciones
- (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.
Open Access - (2019). TIAR controls mitotic entry, maintains genome stability and retains CDK1 in checkpoint bodies.. EMBO Rep 20, pii: e46224.
- (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). 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.
- (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.
- (2015). Replication stress caused by low MCM expression limits fetal erythropoiesis and hematopoietic stem cell functionality.. Nat Communications 6, 8548.
- (2015). Deregulated expression of Cdc6 in the skin facilitates papilloma formation and affects the hair growth cycle.. Cell Cycle 14, 3897-3907.
- (2015). Functional reprogramming of polyploidization in megakaryocytes.. Dev Cell 32, 155-167.
- (2015). NSMCE2 suppresses cancer and aging in mice independently of its SUMO ligase activity.. EMBO J 34, 2604-2619.
- (2014). Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells.. Nature 512, 198-202.
- (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.
- (2013). A proteomic characterization of factors enriched at nascent DNA molecules.. Cell Reports 3, 1-12.