My lab aims to understand the basic mechanisms controlling DNA replication in mammalian cells and how disruption of this process leads to genomic instability and cancer.
The maintenance of genome stability relies on the accurate and processive replication of genomic DNA and its dysregulation triggers genomic instability, a major hallmark of cancer.
Cancer cells are indeed characterised by a constitutive defective DNA replication, also known as replication stress, whose nature is still poorly characterised. Understanding how cancer cells perturb their chromosomal DNA replication, while increasing our knowledge of the causes and consequences of genomic instability in cancer, might also pave the way to the identification of synthetic vulnerabilities of cancer cells and novel therapeutic approaches.
My lab is interested in understanding the basic mechanisms that coordinate initiation and progression of DNA replication in mammalian cells, the links with the machinery that assembles nucleosomes at the replication fork and how dysfunctional DNA replication triggers genomic and epigenomic instability in cancer.
Thus, we combine classical cell biology and biochemistry, with state-of-the-art genomic and proteomic approaches to identify and characterise new factors involved in the maintenance of genome and epigenome stability at the replication forks and to search for novel vulnerabilities of cancer cells.
The linker histone H1–BRCA1 axis is a crucial mediator of replication fork stability Ozgencil M, Dullovi A, Christiane Higos RC et al. Life Science Alliance (2023) 6(10) e202301933
POLQ seals post-replicative ssDNA gaps to maintain genome stability in BRCA-deficient cancer cells Belan O, Sebald M, Adamowicz M et al. Molecular Cell (2022) 82(10) 4664-4680.e9
NCOA4 links iron bioavailability to DNA metabolism Federico G, Carrillo F, Dapporto F et al. Cell Reports (2022) 40(10) 111207
Disrupted control of origin activation compromises genome integrity upon destabilization of Polε and dysfunction of the TRP53-CDKN1A/P21 axis Borel V, Boeing S, Van Wietmarschen N et al. Cell Reports (2022) 39(10) 110871
Multiple roles of Pol epsilon in eukaryotic chromosome replication Cvetkovic MA, Ortega E, Bellelli R et al. Biochemical Society Transactions (2022) 50(10) 309-320
Induction of APOBEC3 exacerbates DNA replication stress and chromosomal instability in early breast and lung cancer evolution Venkatesan S, Angelova M, Puttick C et al. Cancer Discovery (2021) 11(10) candisc.0725.2020
RTEL1 Regulates G4/R-Loops to Avert Replication-Transcription Collisions Kotsantis P, Segura-Bayona S, Margalef P et al. Cell Reports (2020) 33(10) 108546
Defective ALC1 nucleosome remodeling confers PARPi sensitization and synthetic lethality with HRD Hewitt G, Borel V, Segura-Bayona S et al. Molecular Cell (2021) 81(10) 767-783.e11
Spotlight on the Replisome: Aetiology of DNA Replication-Associated Genetic Diseases Bellelli R, Boulton SJ Trends in Genetics (2020) (1)
Synthetic Lethality between DNA Polymerase Epsilon and RTEL1 in Metazoan DNA Replication Bellelli R, Youds J, Borel V et al. Cell Reports (2020) 31(10) 107675
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