ABSTRACT
Fanconi anemia (FA) is an autosomal or X-linked recessive disorder characterized by chromosomal instability, bone marrow failure, cancer susceptibility, and a profound sensitivity to agents that produce DNA interstrand cross-link (ICL). To date, 15 genes have been identified that, when mutated, result in FA or an FA-like syndrome. It is believed that cellular resistance to DNA interstrand cross-linking agents requires all 15 FA or FA-like proteins. Here, we review our current understanding of how these FA proteins participate in ICL repair and discuss the molecular mechanisms that regulate the FA pathway to maintain genome stability.
Subject(s)
Humans , DNA Damage , DNA Repair , Exodeoxyribonucleases , Genetics , Metabolism , Fanconi Anemia , Genetics , Metabolism , Pathology , Fanconi Anemia Complementation Group N Protein , Fanconi Anemia Complementation Group Proteins , Genetics , Metabolism , Nuclear Proteins , Genetics , Metabolism , Recombinases , Genetics , Metabolism , Tumor Suppressor Proteins , Genetics , Metabolism , UbiquitinationABSTRACT
<p><b>OBJECTIVE</b>To investigate the possible relationship between defects in the FA/BRCA pathway of genomic stability and potential pathogenesis of T and B cell lymphoma.</p><p><b>METHODS</b>Nineteen cell lines derived from diverse subtypes of lymphoma for possible FA pathway defects were screened.</p><p><b>RESULTS</b>No defect in FANCD2 ubiquitination was observed. However, the FANCN protein was absent in cell lines HT and Sudhl4. This absence was correlated with enhanced MMC-induced G2 arrest, growth inhibition and high chromosomal breakage rate in both cell lines. In addition, in exon-5a of FANCN gene, a mutation of c.1769 C>T, p. A590V was found in cell line HT, but not in cell line Sudhl4.</p><p><b>CONCLUSION</b>This mutation may be the reason causing the absence of the FANCN protein expression or making the protein unstable and losing its function.</p>