The Small Business Administration maintains the Dynamic Small Business Search (DSBS) database. As a small business registers in the System for Award Management, there is an opportunity to fill out the small business profile. The information provided populates DSBS. DSBS is another tool contracting officers use to identify potential small business contractors for upcoming contracting opportunities. Small businesses can also use DSBS to identify other small businesses for teaming and joint venturing.

Asterisks indicate statistically significant differences using a chi-squared test (***p

Structural variants (SVs) are known to play important roles in a variety of cancers, but their origins and functional consequences are still poorly understood. The nonrandom distributions of these variants across tumour genomes are often assumed to reflect selective processes, but, as with single nucleotide variants, SV mutation rates often reflect the underlying chromatin and other features at a locus. Inferring which SVs may be under selection in tumourigenesis therefore remains challenging, though identifying such variants may lead to new diagnostic and therapeutic targets. Many SVs are thought to emerge via errors in the repair processes following DNA double strand breaks (DSBs) and a variety of studies have experimentally measured DSB frequencies across the genome in cell lines. Using these data we derive the first quantitative genome-wide models of DSB susceptibility, based upon underlying chromatin and sequence features. These models provide high predictive accuracy and novel insights into the mutational mechanisms generating DSBs. Models trained in one cell type can be successfully applied to others, but a substantial proportion of DSBs appear to reflect cell type specific processes. We also show that regions harboring unusually high tumour SV breakpoint frequencies occur within well modeled regions of the genome but often display DSB frequencies inconsistent with DSB model predictions. Using model predictions as a proxy for susceptibility to DSBs in tumours, many SV hotspots appear to be poorly explained by selectively neutral mutational bias alone. A substantial number of hotspots show unexpectedly high SV breakpoint frequencies given their predicted susceptibility to mutation, and are therefore credible targets of positive selection in tumours. These putatively positively selected hotspots are enriched for genes previously shown to be oncogenic. In contrast, several hundred regions across the genome show unexpectedly low levels of SVs, given their relatively high susceptibility to mutation. These novel 'coldspot' regions appear to be subject to purifying selection in tumours and are enriched for active promoters and enhancers. We conclude that models of DSB susceptibility offer a rigorous approach to the inference of SVs putatively subject to selection in tumours.

Double-strand DNA breaks (DSBs) continuously arise and are a source of mutations and chromosomal rearrangements. Here, we present DSBCapture, a sequencing-based method that captures DSBs in situ and directly maps these at single nucleotide resolution enabling the study of DSB origin. DSBCapture shows substantially increased sensitivity and data yield compared to other methods. Employing DSBCapture, we uncovered a striking relationship between DSBs and elevated transcription within nucleosome-depleted chromatin. 6 library samples, 75 base pairs (50 bp for the EcoRV library) custom protocol (DSBCapture or BLESS) sequenced as paired-end reads on Illumina NextSeq 500 (MiSeq for EcoRV library): 1 replicate for the EcoRV library, 1 replicate for the library coming from the U2OS AID-DlvA cell line with AsiSI restriction enzyme, 2 replicates for the BREAk-seq NHEK libraries and 2 replicates for the BLESS NHEK libraries. 4 RNA-Seq library samples from HEK Gibco cells, single-end sequencing on the Illumina NextSeq 500, 75 base pairs.

Yearly citation counts for the publication titled "Accumulation of DSBs in γ-H2AX domains fuel chromosomal aberrations".

This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp

Explore the historical Whois records related to dsbs.co.uk (Domain). Get insights into ownership history and changes over time.

DNA nucleases EXO1 and DNA2 function redundantly in yeast (Zhu et al. 2008) and humans (Nimonkar et al. 2011) in long-range resection of DNA double-strand breaks (DSBs). Both DNA nucleases act after short 3' ssDNA overhangs are created by the initial resection of DNA DSBs mediated by MRE11A and RBBP8 (CtIP). The roles of BLM (Bloom syndrome helicase) and WRN (Werner syndrome helicase) in facilitation of EXO1- or DNA2-mediated resection of DNA DSBs are also redundant.

EXO1 possesses an intrinsic 5'->3' exonuclease activity. The ATPase activity of BLM DNA helicase is not required for EXO1 catalytic activity, but BLM increases the affinity of EXO1 for DNA ends (Nimonkar et al. 2008). WRN can also positively affect EXO1 exonuclease activity, although the mechanism is not clear (Sturzenegger et al. 2014).

The DNA endonuclease DNA2 has to form a complex with either BLM (Nimonkar et al. 2011) or WRN (Sturzenegger et al. 2014) in order to perform a 5'->3' directed resection of DNA DSBs. BLM forms an evolutionarily conserved complex with TOP3A, RMI1 and RMI2, known as the STR complex in yeast (Zhu et al. 2008) and the BTB or BTRR complex in humans. The entire BTRR complex participates in the activation of DNA2-mediated resection of DNA DSBs (Sturzenegger et al. 2014).

While ATR signaling may be detectable in the absence of long-range resection of DNA DSBs by EXO1 or DNA2 (Eid et al. 2010), EXO1 or DNA2 activity may be necessary to achieve biologically meaningful level of ATR activation (Gravel et al. 2008).

BRIP1 (BACH1, FANCJ) is a DNA helicase recruited to DNA DSBs by interaction with BRCA1 (Cantor et al. 2001) and BLM (Suhasini et al. 2011). BRIP1 is necessary for BRCA1-mediated homology-directed repair of DNA DSBs, and BRIP1 loss-of-function mutations are found in familial breast cancer (Cantor et al. 2001, Litman et al. 2005). The exact role of BRIP1 in DNA repair is not completely clear. BRIP1 is needed for the successful formation of RPA foci and, subsequently, RAD51 foci (Xie et al. 2012). The available evidence suggest that it cooperates with BLM in unwinding of DNA DSBs during resection (Suhasini et al. 2011, Sarkies et al. 2012), and may be especially important for unwinding of DNA that contains oxidative damage (Suhasini et al. 2009).

Activated ATM phosphorylates a number of proteins involved in the DNA damage checkpoint and DNA repair (Thompson and Schild 2002, Ciccia and Elledge 2010), thereby triggering and coordinating accumulation of DNA DSB repair proteins in nuclear foci known as ionizing radiation-induced foci (IRIF). While IRIFs include chromatin regions kilobases away from the actual DSB site, this Reactome pathway represents simplified foci and events that happen proximal to the DNA DSB ends. In general, proteins localizing to the nuclear foci in response to ATM signaling are cooperatively retained at the DNA DSB site, forming a positive feedback loop and amplifying DNA damage response (Soutoglou and Misteli 2008).

Activated ATM phosphorylates the NBN (NBS1) subunit of the MRN complex (MRE11A:RAD50:NBN) (Gatei et al. 2000), as well as the nucleosome histone H2AFX (H2AX) on serine residue S139, producing gamma-H2AFX (gamma-H2AX) containing nucleosomes (Rogakou et al. 1998, Burma et al. 2001). H2AFX is phosphorylated on tyrosine 142 (Y142) under basal conditions (Xiao et al. 2009). After ATM-mediated phosphorylation of H2AFX on S139, tyrosine Y142 has to be dephosphorylated by EYA family phosphatases in order for the DNA repair to proceed and to avoid apoptosis induced by DNA DSBs (Cook et al. 2009). Gamma-H2AFX recruits MDC1 to DNA DSBs (Stucki et al. 2005). After ATM phosphorylates MDC1 (Liu et al. 2012), the MRN complex, gamma-H2AFX nucleosomes, and MDC1 serve as a core of the nuclear focus and a platform for the recruitment of other proteins involved in DNA damage signaling and repair (Lukas et al. 2004, Soutoglou and Misteli 2008).

RNF8 ubiquitin ligase binds phosphorylated MDC1 (Kolas et al. 2007) and, in cooperation with HERC2 and RNF168 (Bekker-Jensen et al. 2010, Campbell et al. 2012), ubiquitinates H2AFX (Mailand et al. 2007, Huen et al. 2007, Stewart et al. 2009, Doil et al. 2009) and histone demethylases KDM4A and KDM4B (Mallette et al. 2012).

Ubiquitinated gamma-H2AFX recruits UIMC1 (RAP80), promoting the assembly of the BRCA1-A complex at DNA DSBs. The BRCA1-A complex consists of RAP80, FAM175A (Abraxas), BRCA1:BARD1 heterodimer, BRCC3 (BRCC36), BRE (BRCC45) and BABAM1 (MERIT40, NBA1) (Wang et al. 2007, Wang and Elledge 2007)

Ubiquitin mediated degradation of KDM4A and KDM4B allows TP53BP1 (53BP1) to associate with histone H4 dimethylated on lysine K21 (H4K20Me2 mark) by WHSC1 at DNA DSB sites (Pei et al. 2011).

Once recruited to DNA DSBs, both BRCA1:BARD1 heterodimers and TP53BP1 are phosphorylated by ATM (Cortez et al. 1999, Gatei et al. 2000, Kim et al. 2006, Jowsey et al. 2007), which triggers recruitment and activation of CHEK2 (Chk2, Cds1) (Wang et al. 2002, Wilson and Stern 2008, Melchionna et al. 2000).

Depending on the cell cycle stage, BRCA1 and TP53BP1 competitively promote either homology directed repair (HDR) or nonhomologous end joining (NHEJ) of DNA DSBs. HDR through homologous recombination repair (HRR) or single strand annealing (SSA) is promoted by BRCA1 in association with RBBP8 (CtIP), while NHEJ is promoted by TP53BP1 in association with RIF1 (Escribano-Diaz et al. 2013).

The Norwegian Directorate for Civil Protection's WFS services include a number of themes: Fire stations (2 variants), Fire control rooms ("110") and their districts, Intermunicipal fire services, Norwegian Civil Defence district offices, Norwegian Civil Defence districts.

For more information on these themes, see metadata on the relevant downloadable datasets.

The difference between the two Fire station variants is that one is symbolized according to main station/local station/depot, while the other is symbolised according to whether the station is staffed 24/7, during work hours or not on a regular basis.

Protein-Protein, Genetic, and Chemical Interactions for Stefanovie B (2020):DSS1 interacts with and stimulates RAD52 to promote the repair of DSBs. curated by BioGRID (https://thebiogrid.org); ABSTRACT: The proper repair of deleterious DNA lesions such as double strand breaks prevents genomic instability and carcinogenesis. In yeast, the Rad52 protein mediates DSB repair via homologous recombination. In mammalian cells, despite the presence of the RAD52 protein, the tumour suppressor protein BRCA2 acts as the predominant mediator during homologous recombination. For decades, it has been believed that the RAD52 protein played only a back-up role in the repair of DSBs performing an error-prone single strand annealing (SSA). Recent studies have identified several new functions of the RAD52 protein and have drawn attention to its important role in genome maintenance. Here, we show that RAD52 activities are enhanced by interacting with a small and highly acidic protein called DSS1. Binding of DSS1 to RAD52 changes the RAD52 oligomeric conformation, modulates its DNA binding properties, stimulates SSA activity and promotes strand invasion. Our work introduces for the first time RAD52 as another interacting partner of DSS1 and shows that both proteins are important players in the SSA and BIR pathways of DSB repair.

Protein-Protein, Genetic, and Chemical Interactions for Lazzaro F (2008):Histone methyltransferase Dot1 and Rad9 inhibit single-stranded DNA accumulation at DSBs and uncapped telomeres. curated by BioGRID (https://thebiogrid.org); ABSTRACT: Cells respond to DNA double-strand breaks (DSBs) and uncapped telomeres by recruiting checkpoint and repair factors to the site of lesions. Single-stranded DNA (ssDNA) is an important intermediate in the repair of DSBs and is produced also at uncapped telomeres. Here, we provide evidence that binding of the checkpoint protein Rad9, through its Tudor domain, to methylated histone H3-K79 inhibits resection at DSBs and uncapped telomeres. Loss of DOT1 or mutations in RAD9 influence a Rad50-dependent nuclease, leading to more rapid accumulation of ssDNA, and faster activation of the critical checkpoint kinase, Mec1. Moreover, deletion of RAD9 or DOT1 partially bypasses the requirement for CDK1 in DSB resection. Interestingly, Dot1 contributes to checkpoint activation in response to low levels of telomere uncapping but is not essential with high levels of uncapping. We suggest that both Rad9 and histone H3 methylation allow transmission of the damage signal to checkpoint kinases, and keep resection of damaged DNA under control influencing, both positively and negatively, checkpoint cascades and contributing to a tightly controlled response to DNA damage.

This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp

Protein-Protein, Genetic, and Chemical Interactions for D'Alessandro G (2018):BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment. curated by BioGRID (https://thebiogrid.org); ABSTRACT: DNA double-strand breaks (DSBs) are toxic DNA lesions, which, if not properly repaired, may lead to genomic instability, cell death and senescence. Damage-induced long non-coding RNAs (dilncRNAs) are transcribed from broken DNA ends and contribute to DNA damage response (DDR) signaling. Here we show that dilncRNAs play a role in DSB repair by homologous recombination (HR) by contributing to the recruitment of the HR proteins BRCA1, BRCA2, and RAD51, without affecting DNA-end resection. In S/G2-phase cells, dilncRNAs pair to the resected DNA ends and form DNA:RNA hybrids, which are recognized by BRCA1. We also show that BRCA2 directly interacts with RNase H2, mediates its localization to DSBs in the S/G2 cell-cycle phase, and controls DNA:RNA hybrid levels at DSBs. These results demonstrate that regulated DNA:RNA hybrid levels at DSBs contribute to HR-mediated repair.

Over the period shown, the revenue generated by DSB (short for Danske Statsbaner) fluctuated slightly. In 2014, the government-owned railway company reached its highest value, of roughly **** billion Danish kroner. The revenue decreased to just under **** billion Danish kroner in 2020. Similarly, the number of customers of Danske Statsbaner fluctuated as well.

Routes and train stations served by DSB

In the middle of the **** century, the first train route in Denmark was inaugurated between the stations Copenhagen and Roskilde. Further sections opened gradually. DSB was founded in 1885 and bought up these routes by and by. The railway company serves more than *** train stations in Denmark, Sweden, and Germany, although the amount steadily decreased in recent years.

Importance of railway transportation in Denmark

Compared to the turnover of other transportation means, railway transportation in Denmark is not among the highest. In 2017, railways ranked seventh among different modes of transport, generating roughly *** billion euros. In comparison, the revenue of sea transportation amounted to more than ** billion euros.

The recruitment of RNF168, an E3 ubiquitin ligase, to DNA double-strand breaks (DSBs) is facilitated by the interaction of RNF168 with the UBE2N:UBE2V2 (UBC13:MMS2) complex, which serves as the E2 ubiquitin ligase for both RNF8 and RNF168. In addition, because the two RNF168 ubiquitin interaction motifs (UIMs) are needed for the accumulation of RNF168 at DSBs, the initial ubiquitination of H2AFX (H2AX) histones by RNF8 is likely involved in RNF168 recruitment to DSBs. Inactivating mutations in both RNF168 alleles are responsible for the RIDDLE (radiosensitivity, immunodeficiency, dysmorphic features and learning difficulties) syndrome (Stewart et al. 2009, Doil et al. 2009, Bekker-Jensen et al. 2010, Campbell et al. 2012, Mattiroli et al. 2012).

This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp

Protein-Protein, Genetic, and Chemical Interactions for An L (2018):RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing repair. curated by BioGRID (https://thebiogrid.org); ABSTRACT: Unrestrained 53BP1 activity at DNA double-strand breaks (DSBs) hampers DNA end resection and upsets DSB repair pathway choice. RNF169 acts as a molecular rheostat to limit 53BP1 deposition at DSBs, but how this fine balance translates to DSB repair control remains undefined. In striking contrast to 53BP1, ChIP analyses of AsiSI-induced DSBs unveiled that RNF169 exhibits robust accumulation at DNA end-proximal regions and preferentially targets resected, RPA-bound DSBs. Accordingly, we found that RNF169 promotes CtIP-dependent DSB resection and favors homology-mediated DSB repair, and further showed that RNF169 dose-dependently stimulates single-strand annealing repair, in part, by alleviating the 53BP1-imposed barrier to DSB end resection. Our results highlight the interplay of RNF169 with 53BP1 in fine-tuning choice of DSB repair pathways.

This event has been computationally inferred from an event that has been demonstrated in another species.

The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.

More details and caveats of the event inference in Reactome. For details on PANTHER see also: http://www.pantherdb.org/about.jsp

DSBs were mapped genome-wide by ssDNA enrichment in cdc6-mn replication comprimsied strains. We mapped DSB sites by detecting DSB-associated ssDNA enrichment on microarrays. To test the role of DNA replication in DSB formation, we mapped ssDNA in a cdc6-mn replication depleted strain. ssDNA was isolated from cells after 5 hours in sporulation medium. As a reference, ssDNA isolated from cells at 0 hrs in sporulation medium prior to DSB formation was differentially labeled and co-hybridized to the same array. For each experiment, we have submitted biological replicates that were hybridized to separate arrays. For each experiment a dye swap was performed and shown to have no effect on the data observed, although not all experiments in this series include the dye swap sample (we have included only two representative experiments for each strain).