Abstract:
:Although RNA and RNA-binding proteins have been linked to double-strand breaks (DSBs), little is known regarding their roles in the cellular response to DSBs and, if any, in the repair process. Here, we provide direct evidence for the presence of RNA-DNA hybrids at DSBs and suggest that binding of RNA to DNA at DSBs may impact repair efficiency. Our data indicate that the RNA-unwinding protein DEAD box 1 (DDX1) is required for efficient DSB repair and cell survival after ionizing radiation (IR), with depletion of DDX1 resulting in reduced DSB repair by homologous recombination (HR). While DDX1 is not essential for end resection, a key step in homology-directed DSB repair, DDX1 is required for maintenance of the single-stranded DNA once generated by end resection. We show that transcription deregulation has a significant effect on DSB repair by HR in DDX1-depleted cells and that RNA-DNA duplexes are elevated at DSBs in DDX1-depleted cells. Based on our combined data, we propose a role for DDX1 in resolving RNA-DNA structures that accumulate at DSBs located at sites of active transcription. Our findings point to a previously uncharacterized requirement for clearing RNA at DSBs for efficient repair by HR.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Li L,Germain DR,Poon HY,Hildebrandt MR,Monckton EA,McDonald D,Hendzel MJ,Godbout Rdoi
10.1128/MCB.00415-16subject
Has Abstractpub_date
2016-10-28 00:00:00pages
2794-2810issue
22eissn
0270-7306issn
1098-5549pii
MCB.00415-16journal_volume
36pub_type
杂志文章abstract::Inactivation of DNA mismatch repair by mutation or by transcriptional silencing of the MLH1 gene results in genome instability and cancer predisposition. We recently found (P. V. Shcherbakova and T. A. Kunkel, Mol. Cell. Biol. 19:3177-3183, 1999) that an elevated spontaneous mutation rate can also result from increase...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.3.940-951.2001
更新日期:2001-02-01 00:00:00
abstract::An elastase-human growth hormone (hGH) fusion gene containing 205 base pairs of elastase 5' flanking region is expressed exclusively in pancreatic acinar cells of transgenic mice. This paper shows that the promoter region (-72 to +8) and the enhancer (-205 to -73) function independently of each other. The elastase enh...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.10.3466
更新日期:1987-10-01 00:00:00
abstract::Intron-encoded U17a and U17b RNAs are members of the H/ACA-box class of small nucleolar RNAs (snoRNAs) participating in rRNA processing and modification. We have investigated the organization and expression of the U17 locus in human cells and found that intronic U17a and U17b sequences are transcribed as part of the t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.8.4509
更新日期:1998-08-01 00:00:00
abstract::Reaper (RPR), HID, and GRIM activate apoptosis in cells programmed to die during Drosophila development. We have previously shown that transient overexpression of RPR in the lepidopteran SF-21 cell line induces apoptosis and that members of the inhibitor of apoptosis (IAP) family of antiapoptotic proteins can inhibit ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.6.3300
更新日期:1998-06-01 00:00:00
abstract::A retroviral vector system was developed to study the retrotransposition of RNAs lacking all cis-acting sequences required for normal retroviral replication. Our experiments indicate that such RNAs can be encapsidated in retroviral proteins, reverse transcribed, and integrated to form functional cDNA genes in infected...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.6.2328
更新日期:1988-06-01 00:00:00
abstract::The functional importance of the two clusters of positively charged amino acids which flank the hydrophobic membrane-anchoring sequence of polyomavirus middle T (mT) protein has been investigated by using site-directed mutagenesis. A clear asymmetry was apparent. No effect on transformation was seen following multiple...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.11.5050
更新日期:1992-11-01 00:00:00
abstract::GIPC is a PDZ protein located on peripheral endosomes that binds to the juxtamembrane region of the TrkA nerve growth factor (NGF) receptor and has been implicated in NGF signaling. We establish here that endogenous GIPC binds to the C terminus of APPL, a Rab5 binding protein, which is a marker for signaling endosomes...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00305-06
更新日期:2006-12-01 00:00:00
abstract::Despite distinct dissimilarities, diverse cancers express several common protumorigenic traits. We present here evidence that the proapoptotic protein Par-4 utilizes one such common tumorigenic trait to become selectively activated and induce apoptosis in cancer cells. Elevated protein kinase A (PKA) activity noted in...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.3.1146-1161.2005
更新日期:2005-02-01 00:00:00
abstract::MIA/CD-RAP is a small, soluble protein secreted from malignant melanoma cells and from chondrocytes. Recent evidence has identified MIA/CD-RAP as the prototype of a small family of extracellular proteins adopting an SH3 domain-like fold. It is thought that interaction between MIA/CD-RAP and specific epitopes in extrac...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.5.1438-1445.2002
更新日期:2002-03-01 00:00:00
abstract::The HMG box containing protein UBF binds to the promoter of vertebrate ribosomal repeats and is required for their transcription by RNA polymerase I in vitro. UBF can also bind in vitro to a variety of sequences found across the intergenic spacer in Xenopus and mammalian ribosomal DNA (rDNA) repeats. The high abundanc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.2.657-668.2002
更新日期:2002-01-01 00:00:00
abstract::The Swi5 zinc finger and the Pho2 homeodomain DNA-binding proteins bind cooperatively to the HO promoter. Pho2 (also known as Bas2 or Grf10) activates transcription of diverse genes, acting with multiple distinct DNA-binding proteins. We have performed a genetic screen to identify amino acid residues in Swi5 that are ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.11.6436
更新日期:1998-11-01 00:00:00
abstract::When herpes simplex virus infects permissive cells, the viral regulatory protein VP16 forms a specific complex with HCF-1, a preexisting nuclear protein involved in cell proliferation. The majority of HCF-1 in the cell is a complex of associated amino (HCF-1(N))- and carboxy (HCF-1(C))-terminal subunits that result fr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.18.6721-6730.2000
更新日期:2000-09-01 00:00:00
abstract::Transcriptional coactivator with PDZ-binding motif (TAZ) physically interacts with a variety of transcription factors and modulates their activities involved in cell proliferation and mesenchymal stem cell differentiation. TAZ is highly expressed in the kidney, and a deficiency of this protein results in multiple rena...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00392-12
更新日期:2012-12-01 00:00:00
abstract::Cells of Candida albicans WO-1 spontaneously switch between a white and opaque CFU, and this phase transition involves a dramatic change in cellular phenotype. By using a differential hybridization screen, an opaque-specific cDNA, Op1a, which represents the transcript of a gene regulated by switching, has been isolate...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.7.2997
更新日期:1992-07-01 00:00:00
abstract::The molecular mechanisms underlying lymphatic vascular development and function are not well understood. Recent studies have suggested a role for endothelial cell (EC) mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) in developmental angiogenesis and atherosclerosis. Here, we show that constitutive los...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01121-15
更新日期:2016-05-31 00:00:00
abstract::We studied RNA polymerase I transcription in cells transfected with a plasmid, prHuTK, containing the herpes simplex virus tk gene fused to a human rRNA promoter. Primer extension analysis of tk RNA isolated from COS cells transfected with prHuTK reveals that transcription from the RNA polymerase I promoter is highly ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.2.352
更新日期:1985-02-01 00:00:00
abstract::Host cell cycle genes provide important functions to retroviruses and retroviruslike elements. To define some of these functions, the cell cycle dependence of transposition of the yeast retroviruslike element Ty3 was examined. Ty3 is unique among retroviruslike elements because of the specificity of its integration, w...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.12.8229
更新日期:1994-12-01 00:00:00
abstract::The retinoblastoma binding protein 1 (RBP1) appears to be an important factor in the repression of E2F-dependent transcription by the retinoblastoma protein (pRB) family. The recent identification of the breast carcinoma associated antigen (BCAA) as an RBP1-like protein led us to investigate its biological properties ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.5.1917-1931.2006
更新日期:2006-03-01 00:00:00
abstract::Platelet-derived growth factor alpha receptor (PDGF alpha R) is a transmembrane tyrosine kinase receptor for all three existing PDGF isoforms, AA, AB, and BB. Transcripts of PDGF alpha R are detected as early as in fertilized mouse eggs and throughout adulthood in a time- and space-specific manner, thereby suggesting ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.2.712
更新日期:1996-02-01 00:00:00
abstract::B-lymphocyte development requires the basic helix-loop-helix proteins encoded by the E2A gene. In this study, the control mechanism of E2A was further explored by disruption of the E2A-related genes, E2-2 and HEB. In contrast to E2A, E2-2 and HEB are not essential for the establishment of the B-cell lineage. However, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.6.2898
更新日期:1996-06-01 00:00:00
abstract::Although the U1 small nuclear ribonucleoprotein particle (snRNP) was the first mRNA-splicing cofactor to be identified, the manner in which it functions in splicing is not precisely understood. Among the information required to understand how U1 snRNP participates in splicing, it will be necessary to know its structur...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.11.4030
更新日期:1987-11-01 00:00:00
abstract::A series of deletion mutants spanning the promoter of the adenovirus early-region IV (EIV) gene were tested for transcriptional activity, using both in vitro and in vivo assays. Four distinct domains had additive effects on efficient transcription from the EIV promoter in HeLa whole-cell extracts. The first resided 20...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.7.2578
更新日期:1987-07-01 00:00:00
abstract::The Ste12p transcription factor controls the expression of Ty1 transposable element insertion mutations and genes whose products are required for mating in Saccharomyces cerevisiae. The binding site for Ste12p is a consensus DNA sequence known as a pheromone response element (PRE). Upstream activating sequences (UASs)...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.8.4330
更新日期:1997-08-01 00:00:00
abstract::Hybridization to synthetic oligonucleotides representing conserved regions in the promoter and first intron of several vertebrate beta-actin genes was used to discriminate between what appears to be a single functional beta-actin gene and numerous pseudogenes in the mouse genome. Sequences derived from the 5' end of t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.1.480
更新日期:1988-01-01 00:00:00
abstract::The recruitment of transcriptional coactivators, including histone modifying enzymes, is an important step in transcription regulation. A typical activator is thought to interact with several cofactors, presumably in a sequential manner. The common use of several cofactors raises the question of how activators achieve...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01461-07
更新日期:2008-04-01 00:00:00
abstract::FUD6, a nonphotosynthetic mutant of Chlamydomonas reinhardtii, was previously found to be deficient in the synthesis of subunit IV of the cytochrome b6/f complex, the chloroplast petD gene product (C. Lemaire, J. Girard-Bascou, F.-A. Wollman, and P. Bennoun, Biochim. Biophys. Acta 851:229-238, 1986). The lesion in FUD...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.9.6171
更新日期:1994-09-01 00:00:00
abstract::Cdc25A is a cell cycle-activating phosphatase, and its overexpression in breast cancers has been shown to correlate with poor prognosis. Most recent studies related to Cdc25A and tumor progression have focused on its role in regulating cell cycle progression. However, less is known about how Cdc25A modulates the metas...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.05523-11
更新日期:2011-08-01 00:00:00
abstract::RSC is an essential chromatin remodeling complex in Saccharomyces cerevisiae that performs central roles in transcriptional regulation and cell cycle progression. Here we identify Htl1 as a novel factor that associates with the RSC complex both physically and functionally. We isolated HTL1 through a genetic screen for...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.23.8165-8174.2002
更新日期:2002-12-01 00:00:00
abstract::RNA editing in trypanosomes has been proposed to occur through transesterification or endonuclease cleavage and RNA ligation reactions. Both models involve a chimeric intermediate in which a guide RNA (gRNA) is joined through its 3' oligo(U) tail to an editing site of the corresponding mRNA. Velocity centrifugation of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.6.2925
更新日期:1995-06-01 00:00:00
abstract::During investigations on the regulation of the Pax-6 gene, we characterized a cDNA from quail neuroretina showing a 5' untranslated region distinct from that previously described and initiated from an internal promoter. Using RNase protection and primer extension mapping, we localized this second quail Pax-6 promoter,...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.6.3344
更新日期:1995-06-01 00:00:00