Honors & Awards


  • Young Scientist Award in Cancer Research, Pole Rabelais Bioscience, CNRS (2016)
  • Graduate fellowship program, French Cancer Research Association (ARC) (2015)
  • Graduate fellowship program, French League against Cancer (LCC) (2012)

Professional Education


  • Doctor of Philosophy, Universite De Montpellier (2016)
  • Master of Science, Universite De Montpellier (2012)
  • Doctor of Pharmacy, Universite De Constantine (2011)

All Publications


  • Regulation of DNA Replication in Early Embryonic Cleavages GENES Kermi, C., Lo Furno, E., Maiorano, D. 2017; 8 (1)

    Abstract

    Early embryonic cleavages are characterized by short and highly synchronous cell cycles made of alternating S- and M-phases with virtually absent gap phases. In this contracted cell cycle, the duration of DNA synthesis can be extraordinarily short. Depending on the organism, the whole genome of an embryo is replicated at a speed that is between 20 to 60 times faster than that of a somatic cell. Because transcription in the early embryo is repressed, DNA synthesis relies on a large stockpile of maternally supplied proteins stored in the egg representing most, if not all, cellular genes. In addition, in early embryonic cell cycles, both replication and DNA damage checkpoints are inefficient. In this article, we will review current knowledge on how DNA synthesis is regulated in early embryos and discuss possible consequences of replicating chromosomes with little or no quality control.

    View details for DOI 10.3390/genes8010042

    View details for Web of Science ID 000399057100040

    View details for PubMedID 28106858

    View details for PubMedCentralID PMC5295036

  • RAD18 Is a Maternal Limiting Factor Silencing the UV-Dependent DNA Damage Checkpoint in Xenopus Embryos DEVELOPMENTAL CELL Kermi, C., Prieto, S., van der Laan, S., Tsanov, N., Recolin, B., Uro-Coste, E., Delisle, M., Maiorano, D. 2015; 34 (3): 364-372

    Abstract

    In early embryos, the DNA damage checkpoint is silent until the midblastula transition (MBT) because of maternal limiting factors of unknown identity. Here we identify the RAD18 ubiquitin ligase as one such factor in Xenopus. We show, in vitro and in vivo, that inactivation of RAD18 function leads to DNA damage-dependent checkpoint activation, monitored by CHK1 phosphorylation. Moreover, we show that the abundance of both RAD18 and PCNA monoubiquitylated (mUb) are developmentally regulated. Increased DNA abundance limits the availability of RAD18 close to the MBT, thereby reducing PCNA(mUb) and inducing checkpoint derepression. Furthermore, we show that this embryonic-like regulation can be reactivated in somatic mammalian cells by ectopic RAD18 expression, therefore conferring resistance to DNA damage. Finally, we find high RAD18 expression in cancer stem cells highly resistant to DNA damage. Together, these data propose RAD18 as a critical embryonic checkpoint-inhibiting factor and suggest that RAD18 deregulation may have unexpected oncogenic potential.

    View details for DOI 10.1016/j.devcel.2015.06.002

    View details for Web of Science ID 000359495900010

    View details for PubMedID 26212134

  • PIP degron proteins, substrates of CRL4(Cdt2), and not PIP boxes, interfere with DNA polymerase eta and kappa focus formation on UV damage NUCLEIC ACIDS RESEARCH Tsanov, N., Kermi, C., Coulombe, P., van der Laan, S., Hodroj, D., Maiorano, D. 2014; 42 (6): 3692-3706

    Abstract

    Proliferating cell nuclear antigen (PCNA) is a well-known scaffold for many DNA replication and repair proteins, but how the switch between partners is regulated is currently unclear. Interaction with PCNA occurs via a domain known as a PCNA-Interacting Protein motif (PIP box). More recently, an additional specialized PIP box has been described, the « PIP degron », that targets PCNA-interacting proteins for proteasomal degradation via the E3 ubiquitin ligase CRL4(Cdt2). Here we provide evidence that CRL4(Cdt2)-dependent degradation of PIP degron proteins plays a role in the switch of PCNA partners during the DNA damage response by facilitating accumulation of translesion synthesis DNA polymerases into nuclear foci. We show that expression of a nondegradable PIP degron (Cdt1) impairs both Pol η and Pol κ focus formation on ultraviolet irradiation and reduces cell viability, while canonical PIP box-containing proteins have no effect. Furthermore, we identify PIP degron-containing peptides from several substrates of CRL4(Cdt2) as efficient inhibitors of Pol η foci formation. By site-directed mutagenesis we show that inhibition depends on a conserved threonine residue that confers high affinity for PCNA-binding. Altogether these findings reveal an important regulative role for the CRL4(Cdt2) pathway in the switch of PCNA partners on DNA damage.

    View details for DOI 10.1093/nar/gkt1400

    View details for Web of Science ID 000334758600027

    View details for PubMedID 24423875

    View details for PubMedCentralID PMC3973308