Genome Surveillance and Stability

Molecular bases of human diseases

Our group is generally interested in the regulation of the DNA Damage Response (DDR), and in particular in its regulation during the early steps of embryonic development. The main function of the DDR is to slow down, or arrest cell prolferation in the presence of DNA lesions (DNA breaks, telomer integrity, replication forks stall) so to avoid cell division in the presence of DNA damage and therefore avoid the propagation of mutations that are drivers of genomic instability. A strong genomic instability is a feature of cancer cells (telomeric fusions, trabnsocations, duplications, deletions). To date it is admitted that the majority of sporadic tumours are the consequence of mutations in DDR genes, which can also lead to the development of genetic diseases. Hence the DDR is currently considered as a major barrier to malignat transformation playing a key role in maintenace of genomic stability.


Waqar Ali
Waqar ALI

Antoine AZE

James Hutchins

Mouhamed Idrissou


Adeline Augereau

Nathalie Malirat
Nathalie MALIRAT

Yara Bawadi

Alix Bernet


Publications of the team

Detection of endogenous translesion DNA synthesis in single mammalian cells

Egger T, Aze A, Maiorano D

Translesion DNA synthesis-driven mutagenesis in very early embryogenesis of fast cleaving embryos

Lo Furno E., Busseau I., Aze A., Lorenzi C., Saghira C., Danzi M., Zuchner S., Maiorano D.


Studying the DNA damage response in embryonic systems.

Lo Furno E, Recolin B, van der Laan S, Aze A, Maiorano D

Translesion Synthesis or Repair by Specialized DNA Polymerases Limits Excessive Genomic Instability upon Replication Stress.

Maiorano D, El Etri J, Franchet C, Hoffmann JS

Dihydropyrimidinase protects from DNA replication stress caused by cytotoxic metabolites

Jihane Basbous, Antoine Aze, Laurent Chaloin, Rana Lebdy, Dana Hodroj, Cyril Ribeyre, Marion Larroque, Caitlin Shepard, Baek Kim, Alain Pruvost, Jérôme Moreaux, Domenico Maiorano, Marcel Mechali, Angelos Constantinou


Preserving Genome Integrity During the Early Embryonic DNA Replication Cycles.

Kermi C, Aze A, Maiorano D


Recent advances in understanding DNA replication: cell type-specific adaptation of the DNA replication program.

Aze A, Maiorano D

+ Replication and Genome Dynamics

Ddx19 links mRNA nuclear export with progression of transcription and replication and suppresses genomic instability upon DNA damage in proliferating cells

Hodroj, D., Serhal, K., Maiorano, D.

An ATR-dependent function for the Ddx19 RNA helicase in nuclear R-loop metabolism

Hodroj D, Recolin B, Serhal K, Martinez S, Tsanov N, Abou Merhi R, Maiorano D

Regulation of DNA Replication in Early Embryonic Cleavages

Kermi, C., Lo Furno, E., Maiorano, D

Reversible p53 inhibition prevents cisplatin ototoxicity without blocking chemotherapeutic efficacy

Benkafadar N, Menardo J, Bourien J, Nouvian R, François F, Decaudin D, Maiorano D, Puel JL, Wang J.

Chapter 6 -Open Access - Genomic instability of pluripotent stem cells: origins and consequences

Lo Furno, E., van der Laan, S., and Maiorano, D.

Rad18 is a maternal limiting factor that suppresses the UV-dependent DNA damge checkpoint in Xenopus embryos

Kermi, C., Prieto, S., van der Laan, S., Tsanov, N., Recolin, B., Uro-Coste, E., Delisle, M-B., and Maiorano, D.

Regulation of translesion DNA synthesis by PCNA monoubiquitylation and beyond

Tsanov, N., Kermi, C., Delgado, J., Serrano, L., Maiorano D.

Checking the cycle by ERRβ splice variants

Vanacker JM, Maiorano D.

Molecular mechanisms of DNA replication checkpoint activation

Recolin B, van der Laan S, Tsanov N, Maiorano D.

Cell Cycle-Dependent Expression of Dub3, Nanog and the p160 Family of Nuclear Receptor Coactivators (NCoAs) in Mouse Embryonic Stem Cells

van der Laan S, Golfetto E, Vanacker JM, Maiorano D.

Post-translational modifications in embryonic cell cycle

Van der Laan, S., Maiorano, D.

PIP degron proteins, substrates of CRL4Cdt2, and not PIP boxes, interfere with DNA polymerase h and k focus formation upon UV damage

Tsanov, N., Kermi, C., Coulombe, P., Van der Laan, S., Hodroj, D., Maiorano, D.

High Dub3 expression in mouse ESC couples the G1/S checkpoint to pluripotency

Van der Laan, S., Crozet, C., Tsanov, N., and Maiorano, D

Polk in replication checkpoint

Maiorano, D., Hoffmann, JS.

DNA polymerase k-dependent DNA synthesis at stalled replication forks is important for Chk1 activation

Bétous R., Pillaire, M-J, Pierini, L., Van der Laan, S., Recolin B., Ohl-Séguy, E., Guo, C., Niimi, N., Gruz, P., Nohmi, T. Friedberg, E., Cazaux, C., Maiorano, D* and Hoffmann J-S*. * corresponding authors

Role of RPA as sensor in activation of the S-phase checkpoint in Xenopus egg extracts

Recolin, B., Van der Laan, S., and Maiorano, D.

Implication of RPA32 phosphorylation in S-phase checkpoint signalling at replication forks stalled with aphidicolin in Xenopus egg extracts

Recolin, B., Maiorano, D

Regulation of S phase during early embryonic Xenopus development

Recolin, B., Maiorano, D.

XRCC1 interacts with the p58 subunit of DNA Pola-primase and may coordinate DNA repair and replication during S phase.

Levy N, Oehlmann M, Delalande F, Nasheuer HP, Van Dorsselaer A, Schreiber V, De Murcia G, Ménissier-de Murcia J, Maiorano D, Bresson Anne.

Geminin is cleaved by caspase-3 during apoptosis in Xenopus egg extracts

Auziol C, Mechali M, Maiorano D.

+ Replication and Genome Dynamics

A Cdt1-geminin complex licenses chromatin for DNA replication and prevents rereplication during S phase in Xenopus.

Lutzmann M, Maiorano D, Mechali M.

+ Replication and Genome Dynamics

Identification of full genes and proteins of MCM9, a novel, vertebrate-specific member of the MCM2-8 protein family

Lutzmann, M., Maiorano, D., and Méchali, M.

+ Replication and Genome Dynamics

MCM8, a novel DNA helicase which is not required for licensing but functions during processive chromosomal replication in vertebratres.

Maiorano, D., Cuvier, O., Danis, E., and Mechali, M.

+ Replication and Genome Dynamics

Recombinant Cdt1 induces rereplication of G2 nuclei in Xenopus egg extracts

Maiorano, D., Krasinska, L., Lutzmann, M. and Mechali M.

+ Replication and Genome Dynamics

A hypophosphorylated form of RPA34 is a specific component of pre-replication centers.

Françon, P. ; Lemaitre, JM., Dreyer, C. ; Maiorano, D. ; Cuvier, O. and Marcel Méchali.

+ Replication and Genome Dynamics

Crystal Structure of the Coiled-coil Dimerization Motif of Geminin : Structural and Functional Insights on DNA Replication Regulation.

Thepaut, M., Maiorano, D., Guichou, JF., Auge, MT., Dumas, C., Méchali, M., and Padilla, A.

+ Replication and Genome Dynamics

Specification of a DNA replication origin by a transcription complex.

Danis, E., Brodolin, K., Menut, S., Maiorano, D., Girard-Reydet, C. and Marcel Méchali.

+ Replication and Genome Dynamics

Cell cycle regulation of the licensing activity of Cdt1 in Xenopus laevis.

Maiorano, D., Rul, W., and Marcel Mechali

+ Replication and Genome Dynamics

Repression of origin assembly in metaphase depends on inhibition of RLF-B/cdt1 by geminin.

Tada, S., Li, A., Maiorano, D., Méchali, M., and Blow, J.

+ Replication and Genome Dynamics

XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis

Maiorano, D., Moreau, J., and Méchali, M.

+ Replication and Genome Dynamics

Stepwise Regulated Chromatin Assembly of MCM2-7 Proteins.

Maiorano, D., Lemaître, J.M. and Méchali, M.

+ Replication and Genome Dynamics

Initiation of DNA replication in eukaryotes : questioning the origin.

Françon, P., Maiorano, D. and Méchali, M.

+ Replication and Genome Dynamics

Evidence for different MCM subcomplexes with differential binding to chromatin in Xenopus.

Coué, M., Amariglio, F., Maiorano, D., Bocquet, S. and Méchali, M.

+ Replication and Genome Dynamics

Thèses et hdr

Functional characterization of the tolerance to DNA damage of early embryosSubject: 25/11/2019

Defended by Elena Lo Furno on 25/11/2019 under the supervision of Domenico Maiorano


Functional interaction between the lesion tolerance system and the DNA damage checkpoint: implications for genome stability and oncogenesis 14/12/2016

Defended by Chames Kermi on 14/12/2016 under the supervision of Domenico Maiorano