Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression profile in mouse tumor RIF-1 cell line after knockdown of Bre1a (Rnf20) or Bre1b (Rnf40).

ABSTRACT: Mammalian Bre1 complexes (BRE1A/B (RNF20/40) in humans and Bre1a/b (Rnf20/40) in mice) function similarly to their yeast homolog Bre1 as ubiquitin ligases in monoubiquitination of histone H2B. This ubiquitination facilitates methylation of histone H3 at K4 and K79, and accounts for the roles of Bre1 and its homologs in transcriptional regulation. Recent studies by others suggested that Bre1 acts as a tumor suppressor, augmenting expression of select tumor suppressor genes and suppressing select oncogenes. In this study we present an additional mechanism of tumor suppression by Bre1 through maintenance of genomic stability. We track the evolution of genomic instability in Bre1-deficient cells from replication-associated double-strand breaks (DSBs) to specific genomic rearrangements that explain a rapid increase in DNA content and trigger breakage-fusion-bridge cycles. We show that aberrant RNA-DNA structures (R-loops) constitute a significant source of DSBs in Bre1-deficient cells. Combined with a previously reported defect in homologous recombination, generation of R-loops is a likely initiator of replication stress and genomic instability in Bre1-deficient cells. We propose that genomic instability triggered by Bre1 deficiency may be an important early step that precedes acquisition of an invasive phenotype, as we find decreased levels of BRE1A/B and dimethylated H3K79 in testicular seminoma and in the premalignant lesion in situ carcinoma. A cellular modification design type is where a modification of the transcriptome, proteome (not genome) is made, for example RNAi, antibody targeting. Knock down by RNA interference: gene knocked down in RIF-1 cell line cellular_modification_design

ORGANISM(S): Mus musculus

SUBMITTER: Sophia Chernikova

PROVIDER: E-GEOD-34977 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Deficiency in mammalian histone H2B ubiquitin ligase Bre1 (Rnf20/Rnf40) leads to replication stress and chromosomal instability.

Chernikova Sophia B SB Razorenova Olga V OV Higgins John P JP Sishc Brock J BJ Nicolau Monica M Dorth Jennifer A JA Chernikova Diana A DA Kwok Shirley S Brooks James D JD Bailey Susan M SM Game John C JC Brown J Martin JM

Cancer research 20120221 8

Mammalian Bre1 complexes (BRE1A/B (RNF20/40) in humans and Bre1a/b (Rnf20/40) in mice) function similarly to their yeast homolog Bre1 as ubiquitin ligases in monoubiquitination of histone H2B. This ubiquitination facilitates methylation of histone H3 at K4 and K79, and accounts for the roles of Bre1 and its homologs in transcriptional regulation. Recent studies by others suggested that Bre1 acts as a tumor suppressor, augmenting expression of select tumor suppressor genes and suppressing select ...[more]

PMID: 22354749

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Dataset Information

Gene expression profile in mouse tumor RIF-1 cell line after knockdown of Bre1a (Rnf20) or Bre1b (Rnf40).

Publications

Deficiency in mammalian histone H2B ubiquitin ligase Bre1 (Rnf20/Rnf40) leads to replication stress and chromosomal instability.

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