| Autor: |
Labrie Y, St-Laurent Pedneault C, Bouffard F, Bélanger S, Durocher F, Ouellette G, Beauparlant Cj, Plourde Kv |
| Rok vydání: |
2013 |
| Předmět: |
|
| Zdroj: |
Journal of Genetic Syndromes & Gene Therapy. |
| ISSN: |
2157-7412 |
| Popis: |
The integrity of the FANC gene family is essential for the proper reparation of DNA damages. Recently, different FANCC splice variants were identified. We characterized sequence variations and studied the impact of the alternative splicing event FANCCâ7 on DNA repair. The FANCCâ7 transcript is present in all breast cancer lines analyzed. Genomic and complementary DNA sequencing of non-BRCA1/2 individuals was performed to identify sequence variants and alternative transcripts of the FANCC gene. Ribosomal fractions allowed confirming the translation of FANCCâ7 into a functional protein. The variant protein seems to be secluded in the cytoplasm in transfected HEK293T cells following MMC treatments contrary to the FANCC protein that migrates to the nucleus. Performing localization studies, we observed evidences of colocalization of FANCC and FANCCâ7 with BRCA1 in centrosomes of cells. We demonstrated that FANCC deficient cells infected with FANCCâ7 cDNA show a blocking in G2/M in the presence of MMC. Finally, FANCCâ7 is unable to allow the monoubiquitination of FANCD2. This study unravels the incapability of the FANCCâ7 splicing event to permit the reparation of interstrand crosslinks induced by MMC. This work unravels a novel layer of complexity to the understanding of the fascinating FANC-BRCA DNA repair pathway. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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