Francisco Blanco
fblanco
Francisco Blanco
PRINCIPAL INVESTIGATOR
Ikerbasque Research Professor
Address: Bizkaia Science and Technology Park,
building 800, Derio (Bizkaia)
Structural Biology of Cancer Lab

Francisco J Blanco obtained his Bachelor and Doctorate degrees in Chemistry at the Complutense University of Madrid, in years 1988 and 1992. His PhD thesis was supervised by JL Nieto at the Instituto de Estructura de la Materia-CSIC, Madrid. He used Nuclear Magnetic Resonance to characterize the first linear peptides able to fold as β-hairpins in solution. In 1993 he joined L Serrano’s Group at the European Molecular Biology Laboratory (Heidelberg, Germany) and showed that the evolution of a new protein fold from an existing one is unlikely to occur through a series of intermediate folded sequences. In 1997 he moved to R Tycko’s Lab at the National Institutes of Health (Bethesda,USA) and obtained solid state NMR evidence for a helix-loop-helix structure in the HIV-Rev protein in fibrillar state. In 2000 he returned to Madrid to work with M. Rico´s group at the CSIC on the NMR structure of a protein with a novel fold. He was awarded a Ramón y Cajal contract in 2002 and joined the Centro Nacional de Investigaciones Oncológicas to establish and lead the NMR group. He characterized native and engineered homing endonucleases as tools for gene repair, and the solution structure of the Proliferating Cellular Nuclear Antigen (PCNA) ring. Late in 2007 he joined the Structural Biology Unit at the CIC bioGUNE as an Ikerbasque Research Professor to work on the structure-function of protein complexes involved in chromatin remodelling and DNA repair.

The Structural Biology and Cancer Lab primarily uses NMR for biomolecular structural characterization and incorporates complementary structural and functional studies through collaborations. This integrative structural and functional approach is indispensable to understand protein complexes relevant in chromatin remodeling and DNA replication and repair. We study the INhibitor of Growth (ING1-5) family of tumor suppressors, which restrict cell growth and induce apoptosis through transcription regulation. They form interaction networks, binding histone H3 tails and recruiting Histone Acetyl Transferase (HAT) and Histone Deacetylase (HDAC) complexes to the chromatin. The lab has characterized the structure of ING4 as a dimeric protein that recognizes histone H3 trimethylated at lysine 4 through its PlantHomeoDomain (PHD). Structure-sequence alignments suggest that homodimerization of other ING proteins, and even heterodimerization, may occur, especially between the highly homologous ING4 and ING5. The team is characterizing the structure of ING5 and its N-terminal domain, and the possible formation of heterodimers and also is studing the structural and functional implications of ING5 mutants detected in cancer. PCNA is a DNA sliding clamp, an essential factor for DNA replication and repair. It has a ring-shape structure and interacts with many proteins, including ING1. The group found by NMR that some interactions are extremely weak in solution, likely mediated by other factors in the cell. The PCNA associated factor p15 is overexpressed in cancer, with high levels correlating with poor prognosis, and becomes ubiquitylated upon DNA damage and also found that p15 is an intrinsically disordered protein that binds and threads through the PCNA channel with its N- and C-terminal tails remaining disordered at both sides of the ring. P15 binds simultaneously and independently to DNA, suggesting a regulation of PCNA sliding velocity on the DNA. This might facilitate the switch from replicative to translesion synthesis polymerase binding at stalled replication forks. The lab is investigating the structure and binding properties of ubiquitylated p15.