Article
The Fanconi Anemia Pathway Protects Genome Integrity from R-loops
Author/s | García Rubio, María Luisa
Pérez Calero, Carmen Barroso Ceballos, Sonia Inés Tumini, Emanuela Herrera Moyano, Emilia Aguilera López, Andrés |
Department | Universidad de Sevilla. Departamento de Genética |
Publication Date | 2015 |
Deposit Date | 2017-03-14 |
Published in |
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Abstract | Co-transcriptional RNA-DNA hybrids (R loops) cause genome instability. To prevent harmful R loop accumulation, cells have evolved specific eukaryotic factors, one being the BRCA2 double-strand break repair protein. As BRCA2 ... Co-transcriptional RNA-DNA hybrids (R loops) cause genome instability. To prevent harmful R loop accumulation, cells have evolved specific eukaryotic factors, one being the BRCA2 double-strand break repair protein. As BRCA2 also protects stalled replication forks and is the FANCD1 member of the Fanconi Anemia (FA) pathway, we investigated the FA role in R loop-dependent genome instability. Using human and murine cells defective in FANCD2 or FANCA and primary bone marrow cells from FANCD2 deficient mice, we show that the FA pathway removes R loops, and that many DNA breaks accumulated in FA cells are R loop-dependent. Importantly, FANCD2 foci in untreated and MMC-treated cells are largely R loop dependent, suggesting that the FA functions at R loop-containing sites. We conclude that co-transcriptional R loops and R loop-mediated DNA damage greatly contribute to genome instability and that one major function of the FA pathway is to protect cells from R loops. |
Citation | García Rubio, M.L., Pérez Calero, C., Barroso Ceballos, S.I., Tumini, E., Herrera Moyano, E. y Aguilera López, A. (2015). The Fanconi Anemia Pathway Protects Genome Integrity from R-loops. Plos Genetics, 11 (11), e1005674. |
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