title: R-loops and genomic instability in Bre1 (RNF20/40)-deficient cells.
abstract: We have proposed that maintenance of genomic stability may constitute the basis for the tumor-suppressing activity of the Bre1 (RNF20/RNF40) complex. Revisiting the evidence we presented in our recent publication, we discuss the mechanism by which maintenance of genomic stability by the Bre1 complex is achieved through coordination of events during transcription. Among many functions of Bre1, we focus on the two that, when defective, could lead to the formation of R-loops, the RNA:DNA hybrid structures regarded as a major source of genomic instability. Specifically, we discuss the role of Bre1-mediated H2B ubiquitination in the 3'-end processing of replication-associated histone mRNA and in heterochromatic gene silencing and show how disturbance of these two functions may result in the specific pattern of chromosomal abnormalities we observe in the Bre1-depleted cells.
authors: Department of Radiation Oncology, Stanford University, Stanford, CA, USA. sbchernikova@stanford.edu
authors: Sophia B
authors: SB
authors: Chernikova
authors: J Martin
authors: JM
authors: Brown
mesh_terms: D000818:Animals; D016923:Cell Death; D043171:Chromosomal Instability; D033481:Chromosomes, Mammalian / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D020868:Gene Silencing; D042822:Genomic Instability; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009690:Nucleic Acid Conformation; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D006570:Heterochromatin; D006657:Histones; D012333:RNA, Messenger; D004247:DNA; C571257:RNF20 protein, mouse; D044767:Ubiquitin-Protein Ligases