Fanconi anemia C gene product regulates expression of genes involved in differentiation and inflammation.

Abstract:

:Loss of Fanconi anemia (FA) proteins activity by recessive inherited mutations in one of the FA genes leads to a disease characterized by bone marrow failure, myeloid leukemia and DNA damage hypersensitivity. The aim of this work was to improve our understanding of the FA syndrome defining the transcription profile of the FA complementation group C (FANCC)-deficient cells in comparison to their ectopically corrected counterpart using oligonucleotide microarrays. In this way, 49 RNAs have been isolated, which showed a consistent differential pattern of expression among FANCC mutated and corrected cells. The observed specific changes in gene expression suggest that FANCC regulates specifically myeloid differentiation and unmasks a previously unsuspected anti-inflammatory role for the FA proteins. In spite of the DNA damage hypersensitivity of the syndrome, no gene coding for a protein directly involved in DNA repair/damage response was found to be deregulated in our analysis. This observation suggests that FANCC does not directly control genes involved in DNA repair at the transcriptional level, but does not exclude a regulation at the translational or post-translational level, or by protein/protein interactions. The potential role of the differentially expressed genes in FA phenotype as well as a functional- and cellular-based clustering of the identified genes are presented and discussed.

journal_name

Oncogene

journal_title

Oncogene

authors

Zanier R,Briot D,Dugas du Villard JA,Sarasin A,Rosselli F

doi

10.1038/sj.onc.1207677

subject

Has Abstract

pub_date

2004-06-24 00:00:00

pages

5004-13

issue

29

eissn

0950-9232

issn

1476-5594

pii

1207677

journal_volume

23

pub_type

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