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Genetic Instability and Cancer

(Department Molecular Bases of Human Diseases)


Leader: Angelos CONSTANTINOU


From the earliest stages of tumour genesis, deregulated oncogenes induce the formation of DNA lesions during the process of DNA replication. Replication-associated defects can result from chemical alterations in the DNA template, from nucleotide pool imbalance and/or from conflicts between the replication and transcription machineries. Stalled replication forks and DNA lesions induce a variety of surveillance pathways collectively known as the DNA damage response.

We study how cells respond to replication impediments. Our goal is to unveil novel mechanisms that allow DNA replication to overcome obstacles. We believe that these mechanisms are key determinants of tumour growth and resistance to chemotherapies. In recent years, our main focus has been on the molecular function of proteins implicated in Fanconi anaemia, a genetic disorder characterised by congenital abnormalities, bone marrow failure and cancer proneness. FANC proteins are necessary to coordinate the action of molecular machines involved in the rescue of stalled replication forks and in DNA repair. We explore novel mechanisms implicated in the signalling of damaged replication intermediates, and we use proteomic approaches to understand the biology of the replication machinery under stressful conditions.



Group's News


News FANCI/D2 regulate the dynamics of splicing factors

Moriel-Carretero et al.(Constantinou's lab) show that the Fanconi anemia proteins FANCI and FANCD2 associate with the splicing factor SF3B1 and that DNA replication stress induces the FANCI-dependent release of SF3B1 from nuclear speckles. FANCI and FANCD2 prevent accumulation of postcatalytic intron lariats, suggesting that they help coordinate DNA replication and transcription.
Journal of Cell Biology - DOI: 10.1083/jcb.201702136

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Group's publications of the year (2017):

Moriel-Carretero, M., Ovejero, S., Gerus-Durand, M., Vryzas, D., Constantinou, A..
Fanconi anemia FANCD2 and FANCI proteins regulate the nuclear dynamics of splicing factors
(2017), J Cell Biol. : in press
Viziteu E, Klein B, Basbous J, Lin YL, Hirtz C, Gourzones C, Tiers L, Bruyer A, Vincent L, Grandmougin C, Seckinger A, Goldschmidt H, Constantinou A, Pasero P, Hose D, Moreaux J..
RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma
(2017), Leukemia : 31, 10, 2104-2113


All the publications of the group


Name / First name Room Phone status


BASBOUS Jihane 038-039 9815 CR (CNRS) E-mail    Photo  
CONSTANTINOU Angelos 038-039 9814/9907 DR (INSERM) E-mail    Photo  
RIBEYRE Cyril 038-039 9815 CR (CNRS) E-mail    Photo  

   Engineer & Administrative

VIDAL-EYCHENIE Sophie 038-039 9815 TECH (CNRS) E-mail    Photo  


FRATTINI Camilla 038-039 9815 (CNRS) E-mail    Photo  
GERUS-DURAND Marie 038-039 9815 (CNRS) E-mail    Photo  
OVEJERO MERINO Sara 038-039 9815 (CNRS) E-mail    Photo  

   Fixed-term contract

BAPTISTE Julie 038-039 9815 IE (CNRS) E-mail    Photo  

Genetic Instability and Cancer Group

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