Abstract
R-loops, which consist of DNA : RNA hybrids and displaced single-strand DNA, are a major threat to genome stability. We have previously reported that a key Fanconi anemia protein, FANCD2, accumulates on large fragile genes during mild replication stress in a manner depending on R-loops. In this study, we found that FANCD2 suppresses R-loop levels. Furthermore, we identified FANCD2 interactions with RNA processing factors, including hnRNP U and DDX47. Our data suggest that FANCD2, which accumulates with R-loops in chromatin, recruits these factors and thereby promotes efficient processing of long RNA transcripts. This may lead to a reduction in transcription-replication collisions, as detected by PLA between PCNA and RNA Polymerase II, and hence, lowered R-loop levels. We propose that this mechanism might contribute to maintenance of genome stability during mild replication stress.
Keywords:
DDX47; FANCD2; R-loops; hnRNP U; replication stress.
© 2018 Federation of European Biochemical Societies.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Bone Neoplasms / genetics
-
Bone Neoplasms / metabolism
-
Bone Neoplasms / pathology
-
Chromatin / chemistry
-
Chromatin / genetics
-
Chromatin / metabolism
-
DEAD-box RNA Helicases / genetics
-
DEAD-box RNA Helicases / metabolism*
-
DNA Repair
-
DNA Replication*
-
DNA, Neoplasm / chemistry
-
DNA, Neoplasm / genetics
-
DNA, Neoplasm / metabolism
-
Fanconi Anemia Complementation Group D2 Protein / genetics
-
Fanconi Anemia Complementation Group D2 Protein / metabolism*
-
Genomic Instability*
-
Heterogeneous-Nuclear Ribonucleoprotein U / genetics
-
Heterogeneous-Nuclear Ribonucleoprotein U / metabolism*
-
Humans
-
Osteosarcoma / genetics
-
Osteosarcoma / metabolism
-
Osteosarcoma / pathology
-
RNA Polymerase II / genetics
-
RNA Polymerase II / metabolism*
-
RNA Processing, Post-Transcriptional
-
RNA, Neoplasm / chemistry
-
RNA, Neoplasm / genetics
-
RNA, Neoplasm / metabolism*
-
Tumor Cells, Cultured
Substances
-
Chromatin
-
DNA, Neoplasm
-
FANCD2 protein, human
-
Fanconi Anemia Complementation Group D2 Protein
-
Heterogeneous-Nuclear Ribonucleoprotein U
-
RNA, Neoplasm
-
RNA Polymerase II
-
DDX47 protein, human
-
DEAD-box RNA Helicases