CV Science

Domenico MAIORANO PhD Genetics and Cell Biology

Course and current status

1995. PhD, University of Oxford (England, UK). Cell cycle regulation of DNA replication in fission yeast.

1996. Research Assistant, University of Oxford.

1997-2001. Postdoctoral fellow at the Institute Jacques Monod (Paris, France), then at the Institute of Human Genetics of Montpellier (France). Biochemistry of DNA replication in Xenopus in vitro systems.

2001. Staff researcher employed by INSERM at the CNRS Institute of Human Genetics of Montpellier (France)

Since April 2007. Group leader of the "Genome Surveillance and Stability" team at the Institute of Human Genetics of Montpellier (France). Biochemistry and Cell Biology of the DNA damage response.

Membership

Life member of Trinity College, Oxford (England, UK)

Member of Faculty of 1000 Biology “Nuclear Structure and Function Section”

Member of the French Society of Cell Biology

Member of the French Society of Biochemistry and Molecualr Biology

Academic Editor at PloS One

Biography published by Marquis “Who’s Who in the World”, “Who’s Who in Healthcare and Medicine”,  “ Who’s Who in Science and Engineering”.

Scientific summary

My team is interested in the regulation of DNA damage and replication checkpoints (DNA damage response). These surveillance mechanisms are crucial in the maintenance of genomic stability when the integrity of the DNA is compromised. Checkpoint signals are generated in the presence of DNA lesions (such as DNA strands breaks, telomer integrity, replication forks arrest) so to block cell division and activate repair pathways necessary to regenerate the normal state of the DNA. The arrest of DNA replication forks during the S phase of the cell cycle, the exposure to chemical compounds, and endogenous cues, such as free oxygen radicals or the metabolism of the DNA itself, constitute major sources of mutations that continuously threaten the integrity of the genome of the cells of the human body. A strong genomic instability is a hallmark of cancer cells (telomeric fusions, translocations, duplications and deletions) and is responsible for the activation of aberrant genetic programmes. Many genes of the checkpoint pathway have been found mutated in a variety of cancer-susceptibility syndromes, in particular at an aggressive stage.

Although the genes controlling the DNA damage and replication checkpoints are well conserved throughout evolution, a number of genes are only found in vertebrates, and are also found often mutated in several cancers. It is likely that more genes implicated in the regulation of the DNA damage checkpoint, that are not conserved in simple eukaryotes, may exist. We are using a functional screen and a proteomic approach to search for new, vertebrate-specific, checkpoint genes and proteins.We have recently identified one of these, the Ddx19 RNA helicase, that we have shown to be implicated in the DNA damage-dependent resolution of RNA:DNA hybrids (R-loops).

We have also been interested in the regulation of the DNA Damage Responsse during the early steps of embryonic development. We have demonstrated that early Xenopus embryos suppress the DNA replication checkpoiont by constitutively activating the DNA damage tolerance system, that involves translesion DNA synthesis. Further, we have demonstrated that this regulation induces mutations at high rate thus providing a novel mechanisms of genetic variability operating during early embryogenesis.

    We are interested in understanding the molecular mechanism of cancer resistance to therapy by studying the cellular response to DNA damage. We are currently using glioblastoma as a model system, an agressive brain cancer that displays a high resistance to therapeutic treatments.