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