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.
POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication. Mol Cell (2018) 72(1):112-126.e5. PMID: 30217558
Polε Instability Drives Replication Stress, Abnormal Development, and Tumorigenesis. Mol Cell (2018) 70(4):707-721.e7. PMID: 29754823
NCOA4 Deficiency Impairs Systemic Iron Homeostasis. Cell Rep (2016) 14(3):411-421. PMID: 26776506
NCOA4 transcriptional coactivator inhibits activation of DNA replication origins. Mol Cell (2014) 55(1):123-37. PMID: 24910095
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.
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 Discov (2021) (2)
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(7) 767-783.e11
RTEL1 Regulates G4/R-Loops to Avert Replication-Transcription Collisions Kotsantis P, Segura-Bayona S, Margalef P et al. Cell Reports (2020) 33(7)
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(7)
DNA Polymerase Epsilon Deficiency Causes IMAGe Syndrome with Variable Immunodeficiency Logan CV, Murray JE, Parry DA et al. American Journal of Human Genetics (2018) 103(7) 1038-1044
POLE3-POLE4 Is a Histone H3-H4 Chaperone that Maintains Chromatin Integrity during DNA Replication Bellelli R, Belan O, Pye VE et al. Molecular Cell (2018) 72(7) 112-126.e5
Polε Instability Drives Replication Stress, Abnormal Development, and Tumorigenesis Bellelli R, Borel V, Logan C et al. Molecular Cell (2018) 70(7) 707-721.e7
Stabilization of Reversed Replication Forks by Telomerase Drives Telomere Catastrophe Margalef P, Kotsantis P, Borel V et al. Cell (2018) 172(7) 439-453.e14
Oncogene-induced senescence and its evasion in a mouse model of thyroid neoplasia Bellelli R, Vitagliano D, Federico G et al. Molecular and Cellular Endocrinology (2018) 460(7) 24-35For additional publications, please click here