Claspin inhibition leads to fragile site expression

Maria Luisa Focarelli, Samuela Soza, Linda Mannini, Marianna Paulis, Alessandra Montecucco, Antonio Musio

Research output: Contribution to journalArticle

Abstract

Fragile sites are hot spots for sister chromatid exchanges, translocations, deletions, complex rearrangements, and gene amplification. It has been hypothesized that rearrangements at fragile sites derive from unreplicated regions resulting from stalled forks that escape the ATR replication checkpoint. In the present study, we investigated the role of the Claspin (CLSPN) gene, which codes for an adaptor protein in the ATR pathway, during DNA replication stress in human cells. We show that the inhibition of the CLSPN gene leads to both genome instability and fragile site expression. Following aphidicolin treatment, we found a transient increase of Claspin synthesis due to its requirement to checkpoint activation. However, Claspin synthesis decreased after a prolonged aphidicolin treatment. We propose that CLSPN modulation, following an extreme replication block, allows rare cells to escape checkpoint mechanisms and enter mitosis with a defect in genome assembly. Our observations provide the basis for a better understanding of cell cycle checkpoints deregulation in cancer.

Original languageEnglish
Pages (from-to)1083-1090
Number of pages8
JournalGenes Chromosomes and Cancer
Volume48
Issue number12
DOIs
Publication statusPublished - Dec 2009

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Aphidicolin
Sister Chromatid Exchange
Gene Amplification
Genomic Instability
Cell Cycle Checkpoints
DNA Replication
Mitosis
Genes
Genome
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Focarelli, M. L., Soza, S., Mannini, L., Paulis, M., Montecucco, A., & Musio, A. (2009). Claspin inhibition leads to fragile site expression. Genes Chromosomes and Cancer, 48(12), 1083-1090. https://doi.org/10.1002/gcc.20710

Claspin inhibition leads to fragile site expression. / Focarelli, Maria Luisa; Soza, Samuela; Mannini, Linda; Paulis, Marianna; Montecucco, Alessandra; Musio, Antonio.

In: Genes Chromosomes and Cancer, Vol. 48, No. 12, 12.2009, p. 1083-1090.

Research output: Contribution to journalArticle

Focarelli, ML, Soza, S, Mannini, L, Paulis, M, Montecucco, A & Musio, A 2009, 'Claspin inhibition leads to fragile site expression', Genes Chromosomes and Cancer, vol. 48, no. 12, pp. 1083-1090. https://doi.org/10.1002/gcc.20710
Focarelli ML, Soza S, Mannini L, Paulis M, Montecucco A, Musio A. Claspin inhibition leads to fragile site expression. Genes Chromosomes and Cancer. 2009 Dec;48(12):1083-1090. https://doi.org/10.1002/gcc.20710
Focarelli, Maria Luisa ; Soza, Samuela ; Mannini, Linda ; Paulis, Marianna ; Montecucco, Alessandra ; Musio, Antonio. / Claspin inhibition leads to fragile site expression. In: Genes Chromosomes and Cancer. 2009 ; Vol. 48, No. 12. pp. 1083-1090.
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