FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1609541309> ?p ?o ?g. }

• W1609541309 endingPage "83" @default.
• W1609541309 startingPage "4175" @default.
• W1609541309 abstract "Multicellular organisms must have means of preserving their genomic integrity or face catastrophic consequences such as uncontrolled cell proliferation or massive cell death. One response is a modification of nuclear proteins by the addition and removal of polymers of ADP-ribose that modulate the properties of DNA-binding proteins involved in DNA repair and metabolism. These ADP-ribose units are added by poly(ADP-ribose) polymerase (PARP) and removed by poly(ADP-ribose) glycohydrolase. Although budding yeast Saccharomyces cerevisiae does not possess proteins with significant sequence similarity to the human PARP family of proteins, we identified novel small molecule inhibitors against two family members, PARP1 and PARP2, using a cell-based assay in yeast. The assay was based on the reversal of growth inhibition caused by the heterologous expression of either PARP1 or PARP2. Validation of the assay was achieved by showing that the growth inhibition was relieved by a mutation in a single residue in the catalytic site of PARP1 or PARP2 or exposure of yeast to a known PARP1 inhibitor, 6(5H)-phenanthridinone. In separate experiments, when a putative protein regulator of PARP activity, human poly(ADP-ribose) glycohydrolase, was coexpressed with PARP1 or PARP2, yeast growth was restored. Finally, the inhibitors identified by screening the yeast assay are active in a mammalian PARP biochemical assay and inhibit PARP1 and PARP2 activity in yeast cell extracts. Thus, our data reflect the strength of using yeast to identify small molecule inhibitors of therapeutically relevant gene families, including those that are not found in yeast, such as PARP. The resultant inhibitors have two critical uses (a) as leads for drug development and (b) as tools to dissect cellular function." @default.
• W1609541309 created "2016-06-24" @default.
• W1609541309 creator A5005430934 @default.
• W1609541309 creator A5007445328 @default.
• W1609541309 creator A5009550962 @default.
• W1609541309 creator A5012941914 @default.
• W1609541309 creator A5014668074 @default.
• W1609541309 creator A5019621572 @default.
• W1609541309 creator A5025238257 @default.
• W1609541309 creator A5040396412 @default.
• W1609541309 creator A5043511013 @default.
• W1609541309 creator A5051831047 @default.
• W1609541309 creator A5054097550 @default.
• W1609541309 creator A5055302959 @default.
• W1609541309 creator A5062352141 @default.
• W1609541309 creator A5064408494 @default.
• W1609541309 creator A5068763102 @default.
• W1609541309 creator A5078688450 @default.
• W1609541309 date "2001-05-15" @default.
• W1609541309 modified "2023-10-06" @default.
• W1609541309 title "Novel inhibitors of poly(ADP-ribose) polymerase/PARP1 and PARP2 identified using a cell-based screen in yeast." @default.
• W1609541309 cites W1497947649 @default.
• W1609541309 cites W1522255857 @default.
• W1609541309 cites W1541897964 @default.
• W1609541309 cites W1545474197 @default.
• W1609541309 cites W1546643851 @default.
• W1609541309 cites W1605052148 @default.
• W1609541309 cites W1608753926 @default.
• W1609541309 cites W1909198220 @default.
• W1609541309 cites W1966072209 @default.
• W1609541309 cites W1968917541 @default.
• W1609541309 cites W1971953001 @default.
• W1609541309 cites W1980460135 @default.
• W1609541309 cites W1981694306 @default.
• W1609541309 cites W1983795887 @default.
• W1609541309 cites W1990712903 @default.
• W1609541309 cites W1993289350 @default.
• W1609541309 cites W2003737767 @default.
• W1609541309 cites W2004103693 @default.
• W1609541309 cites W2011681733 @default.
• W1609541309 cites W2014150894 @default.
• W1609541309 cites W2021686840 @default.
• W1609541309 cites W2022353228 @default.
• W1609541309 cites W2025393502 @default.
• W1609541309 cites W2025550674 @default.
• W1609541309 cites W2031832448 @default.
• W1609541309 cites W2033761616 @default.
• W1609541309 cites W2040108963 @default.
• W1609541309 cites W2044657175 @default.
• W1609541309 cites W2047049388 @default.
• W1609541309 cites W2047769174 @default.
• W1609541309 cites W2051219590 @default.
• W1609541309 cites W2064714878 @default.
• W1609541309 cites W2075745805 @default.
• W1609541309 cites W2091041535 @default.
• W1609541309 cites W2091512138 @default.
• W1609541309 cites W2092553541 @default.
• W1609541309 cites W2094266637 @default.
• W1609541309 cites W2094991297 @default.
• W1609541309 cites W2096741239 @default.
• W1609541309 cites W2100057937 @default.
• W1609541309 cites W2102360176 @default.
• W1609541309 cites W2112671059 @default.
• W1609541309 cites W2118211036 @default.
• W1609541309 cites W2124259712 @default.
• W1609541309 cites W2140592502 @default.
• W1609541309 cites W2141185701 @default.
• W1609541309 cites W2146678563 @default.
• W1609541309 cites W2149714679 @default.
• W1609541309 cites W2167063739 @default.
• W1609541309 cites W2169333620 @default.
• W1609541309 cites W2171003775 @default.
• W1609541309 cites W2226935353 @default.
• W1609541309 cites W2415111114 @default.
• W1609541309 cites W300133789 @default.
• W1609541309 cites W56295519 @default.
• W1609541309 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11358842" @default.
• W1609541309 hasPublicationYear "2001" @default.
• W1609541309 type Work @default.
• W1609541309 sameAs 1609541309 @default.
• W1609541309 citedByCount "24" @default.
• W1609541309 countsByYear W16095413092013 @default.
• W1609541309 countsByYear W16095413092015 @default.
• W1609541309 countsByYear W16095413092019 @default.
• W1609541309 countsByYear W16095413092020 @default.
• W1609541309 countsByYear W16095413092021 @default.
• W1609541309 countsByYear W16095413092022 @default.
• W1609541309 countsByYear W16095413092023 @default.
• W1609541309 crossrefType "journal-article" @default.
• W1609541309 hasAuthorship W1609541309A5005430934 @default.
• W1609541309 hasAuthorship W1609541309A5007445328 @default.
• W1609541309 hasAuthorship W1609541309A5009550962 @default.
• W1609541309 hasAuthorship W1609541309A5012941914 @default.
• W1609541309 hasAuthorship W1609541309A5014668074 @default.
• W1609541309 hasAuthorship W1609541309A5019621572 @default.
• W1609541309 hasAuthorship W1609541309A5025238257 @default.
• W1609541309 hasAuthorship W1609541309A5040396412 @default.
• W1609541309 hasAuthorship W1609541309A5043511013 @default.

• next