FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2949871277> ?p ?o ?g. }

• W2949871277 abstract "Abstract Interstrand crosslinks (ICLs) represent a highly toxic form of DNA damage that can block essential biological processes including DNA replication and transcription. To combat their deleterious effects all eukaryotes have developed cell cycle-dependent repair strategies that coopt various factors from ‘classical’ DNA repair pathways to resolve such lesions. Here, we report that Trypanosoma brucei , the causative agent of African trypanosomiasis, possesses such systems that show some intriguing differences to those mechanisms expressed in other organisms. Following the identification of trypanosomal homologues encoding for CSB, EXO1, SNM1, MRE11, RAD51 and BRCA2, gene deletion coupled with phenotypic studies demonstrated that all the above factors contribute to this pathogen’s ICL REPAIRtoire with their activities split across two epistatic groups. We show that one network, which encompasses TbCSB, TbEXO1 and TbSNM1, may operate throughout the cell cycle to repair ICLs encountered by transcriptional detection mechanisms while the other relies on homologous recombination enzymes that together may resolve lesions responsible for the stalling of DNA replication forks. By unravelling and comparing the T. brucei ICL REPAIRtoire to those systems found in its host, targets amenable to inhibitor design may be identified and could be used alongside trypanocidal ICL-inducing agents to exacerbate their effects. Author summary Parasites belonging to the Trypanosoma brucei complex cause a human and animal infections collectively known as African trypanosomiasis. Drugs used against these diseases are problematic as medical supervision is required for administration, they are costly, have limited efficacy, may cause unwanted side effects while drug resistance is emerging. Against this backdrop, there is a need for new therapies targeting these neglected tropical diseases. Previous studies have shown compounds that induce DNA interstrand crosslinks (ICLs) formation are effective trypanocidal agents with the most potent invariably functioning as prodrugs. Despite the potential of ICL-inducing compounds to treat African trypanosomiasis little is known about the ICL repair mechanisms expressed by trypanosomes. Using a combination of gene deletion and epistatic analysis we report the first systematic dissection of how ICL repair might operate in T. brucei , a diverged eukaryote. It sheds light on the conservation and divergence of ICL repair in one of only a handful of protists that can be studied genetically, and offers the promise of developing or exploiting ICL-causing agents as new anti-parasite therapies. These findings emphasise the novelty and importance of understanding ICL repair in T. brucei and, more widely, in non-model eukaryotes." @default.
• W2949871277 created "2019-06-27" @default.
• W2949871277 creator A5028932373 @default.
• W2949871277 creator A5048851339 @default.
• W2949871277 date "2019-02-08" @default.
• W2949871277 modified "2023-10-18" @default.
• W2949871277 title "Deciphering the interstrand crosslink DNA repair network expressed by Trypanosoma brucei" @default.
• W2949871277 cites W1602963387 @default.
• W2949871277 cites W1963569841 @default.
• W2949871277 cites W1978737769 @default.
• W2949871277 cites W1978773870 @default.
• W2949871277 cites W1984881284 @default.
• W2949871277 cites W1987395686 @default.
• W2949871277 cites W1987652678 @default.
• W2949871277 cites W1990022215 @default.
• W2949871277 cites W1991297784 @default.
• W2949871277 cites W1993596414 @default.
• W2949871277 cites W1994677283 @default.
• W2949871277 cites W2000142729 @default.
• W2949871277 cites W2004125597 @default.
• W2949871277 cites W2010216792 @default.
• W2949871277 cites W2013132855 @default.
• W2949871277 cites W2016292622 @default.
• W2949871277 cites W2018381709 @default.
• W2949871277 cites W2028490462 @default.
• W2949871277 cites W2028767678 @default.
• W2949871277 cites W2028882157 @default.
• W2949871277 cites W2031414445 @default.
• W2949871277 cites W2032289758 @default.
• W2949871277 cites W2033271892 @default.
• W2949871277 cites W2034905942 @default.
• W2949871277 cites W2040409018 @default.
• W2949871277 cites W2043923950 @default.
• W2949871277 cites W2045429308 @default.
• W2949871277 cites W2054464804 @default.
• W2949871277 cites W2056403222 @default.
• W2949871277 cites W2060186907 @default.
• W2949871277 cites W2062789777 @default.
• W2949871277 cites W2063210197 @default.
• W2949871277 cites W2069119604 @default.
• W2949871277 cites W2070879510 @default.
• W2949871277 cites W2076345136 @default.
• W2949871277 cites W2077451644 @default.
• W2949871277 cites W2077487223 @default.
• W2949871277 cites W2080771970 @default.
• W2949871277 cites W2089207295 @default.
• W2949871277 cites W2090538829 @default.
• W2949871277 cites W2097199426 @default.
• W2949871277 cites W2114180794 @default.
• W2949871277 cites W2117650737 @default.
• W2949871277 cites W2117815751 @default.
• W2949871277 cites W2121150109 @default.
• W2949871277 cites W2125183835 @default.
• W2949871277 cites W2125295721 @default.
• W2949871277 cites W2128680272 @default.
• W2949871277 cites W2128782169 @default.
• W2949871277 cites W2137317157 @default.
• W2949871277 cites W2138425441 @default.
• W2949871277 cites W2139777089 @default.
• W2949871277 cites W2140336382 @default.
• W2949871277 cites W2141451936 @default.
• W2949871277 cites W2141690385 @default.
• W2949871277 cites W2143162088 @default.
• W2949871277 cites W2144840612 @default.
• W2949871277 cites W2146234112 @default.
• W2949871277 cites W2149739510 @default.
• W2949871277 cites W2151062921 @default.
• W2949871277 cites W2151336571 @default.
• W2949871277 cites W2152366070 @default.
• W2949871277 cites W2155714010 @default.
• W2949871277 cites W2157236463 @default.
• W2949871277 cites W2163262261 @default.
• W2949871277 cites W2164109136 @default.
• W2949871277 cites W2167844213 @default.
• W2949871277 cites W2169054397 @default.
• W2949871277 cites W2172044969 @default.
• W2949871277 cites W2179672927 @default.
• W2949871277 cites W2227520693 @default.
• W2949871277 cites W2343455000 @default.
• W2949871277 cites W2346731093 @default.
• W2949871277 cites W2595637745 @default.
• W2949871277 cites W2771808827 @default.
• W2949871277 cites W2801696527 @default.
• W2949871277 cites W2916998141 @default.
• W2949871277 cites W4210387299 @default.
• W2949871277 doi "https://doi.org/10.1101/543975" @default.
• W2949871277 hasPublicationYear "2019" @default.
• W2949871277 type Work @default.
• W2949871277 sameAs 2949871277 @default.
• W2949871277 citedByCount "0" @default.
• W2949871277 crossrefType "posted-content" @default.
• W2949871277 hasAuthorship W2949871277A5028932373 @default.
• W2949871277 hasAuthorship W2949871277A5048851339 @default.
• W2949871277 hasBestOaLocation W29498712771 @default.
• W2949871277 hasConcept C102744134 @default.
• W2949871277 hasConcept C104317684 @default.
• W2949871277 hasConcept C134935766 @default.
• W2949871277 hasConcept C143425029 @default.
• W2949871277 hasConcept C2779012473 @default.
• W2949871277 hasConcept C2779502636 @default.

• next