title: Interplay between Fanconi anemia and homologous recombination pathways in genome integrity.
abstract: The Fanconi anemia (FA) pathway plays a central role in the repair of DNA interstrand crosslinks (ICLs) and regulates cellular responses to replication stress. Homologous recombination (HR), the error-free pathway for double-strand break (DSB) repair, is required during physiological cell cycle progression for the repair of replication-associated DNA damage and protection of stalled replication forks. Substantial crosstalk between the two pathways has recently been unravelled, in that key HR proteins such as the RAD51 recombinase and the tumour suppressors BRCA1 and BRCA2 also play important roles in ICL repair. Consistent with this, rare patient mutations in these HR genes cause FA pathologies and have been assigned FA complementation groups. Here, we focus on the clinical and mechanistic implications of the connection between these two cancer susceptibility syndromes and on how these two molecular pathways of DNA replication and repair interact functionally to prevent genomic instability.
authors.affiliation: Genome Stability and Tumourigenesis Group, Department of Oncology, The CRUK-MRC Oxford Institute for Radiation Oncology University of Oxford, Oxford, UK.
authors.forename: Johanna
authors.initials: J
authors.lastname: Michl
authors.affiliation: Genome Stability and Tumourigenesis Group, Department of Oncology, The CRUK-MRC Oxford Institute for Radiation Oncology University of Oxford, Oxford, UK.
authors.forename: Jutta
authors.initials: J
authors.lastname: Zimmer
authors.affiliation: Genome Stability and Tumourigenesis Group, Department of Oncology, The CRUK-MRC Oxford Institute for Radiation Oncology University of Oxford, Oxford, UK madalena.tarsounas@oncology.ox.ac.uk.
authors.forename: Madalena
authors.initials: M
authors.lastname: Tarsounas
mesh_terms: D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D059765:Homologous Recombination; D006801:Humans; D053858:Metabolic Networks and Pathways; D009369:Neoplasms / Q000235:genetics*
chemical_list: D051856:Fanconi Anemia Complementation Group Proteins; D045643:DNA Repair Enzymes
keywords: DNA damage response; DNA repair; Fanconi anemia; genome stability; homologous recombination; replication stress