Genomic integrity and mitochondrial metabolism defects in Warsaw syndrome cells: a comparison with Fanconi anemia

Roberta Bottega, Silvia Ravera, Luisa M R Napolitano, Viviana Chiappetta, Nicoletta Zini, Barbara Crescenzi, Silvia Arniani, Michela Faleschini, Giuseppe Cortone, Flavio Faletra, Barbara Medagli, Fabio Sirchia, Martina Moretti, Job de Lange, Enrico Cappelli, Cristina Mecucci, Silvia Onesti, Francesca M Pisani, Anna Savoia

Research output: Contribution to journalArticlepeer-review


Warsaw breakage syndrome (WABS), is caused by biallelic mutations of DDX11, a gene coding a DNA helicase. We have recently reported two affected sisters, compound heterozygous for a missense (p.Leu836Pro) and a frameshift (p.Lys303Glufs*22) variant. By investigating the pathogenic mechanism, we demonstrate the inability of the DDX11 p.Leu836Pro mutant to unwind forked DNA substrates, while retaining DNA binding activity. We observed the accumulation of patient-derived cells at the G2/M phase and increased chromosomal fragmentation after mitomycin C treatment. The phenotype partially overlaps with features of the Fanconi anemia cells, which shows not only genomic instability but also defective mitochondria. This prompted us to examine mitochondrial functionality in WABS cells and revealed an altered aerobic metabolism. This opens the door to the further elucidation of the molecular and cellular basis of an impaired mitochondrial phenotype and sheds light on this fundamental process in cell physiology and the pathogenesis of these diseases.

Original languageEnglish
Pages (from-to)5664-5675
Number of pages12
JournalJournal of Cellular Physiology
Issue number8
Publication statusPublished - Aug 2021


  • Abnormalities, Multiple/genetics
  • DEAD-box RNA Helicases/genetics
  • DNA Helicases/genetics
  • Fanconi Anemia/genetics
  • Genomic Instability/genetics
  • Genomics
  • Humans
  • Kearns-Sayre Syndrome/genetics
  • Mitochondrial Myopathies/genetics
  • Mutation/genetics


Dive into the research topics of 'Genomic integrity and mitochondrial metabolism defects in Warsaw syndrome cells: a comparison with Fanconi anemia'. Together they form a unique fingerprint.

Cite this