Matches in SemOpenAlex for { <https://semopenalex.org/work/W2012607520> ?p ?o ?g. }
- W2012607520 endingPage "500" @default.
- W2012607520 startingPage "482" @default.
- W2012607520 abstract "The Mre11-Rad50 complex is highly conserved, yet the mechanisms by which Rad50 ATP-driven states regulate the sensing, processing and signaling of DNA double-strand breaks are largely unknown. Here we design structure-based mutations in Pyrococcus furiosus Rad50 to alter protein core plasticity and residues undergoing ATP-driven movements within the catalytic domains. With this strategy we identify Rad50 separation-of-function mutants that either promote or destabilize the ATP-bound state. Crystal structures, X-ray scattering, biochemical assays, and functional analyses of mutant PfRad50 complexes show that the ATP-induced 'closed' conformation promotes DNA end binding and end tethering, while hydrolysis-induced opening is essential for DNA resection. Reducing the stability of the ATP-bound state impairs DNA repair and Tel1 (ATM) checkpoint signaling in Schizosaccharomyces pombe, double-strand break resection in Saccharomyces cerevisiae, and ATM activation by human Mre11-Rad50-Nbs1 in vitro, supporting the generality of the P. furiosus Rad50 structure-based mutational analyses. These collective results suggest that ATP-dependent Rad50 conformations switch the Mre11-Rad50 complex between DNA tethering, ATM signaling, and 5' strand resection, revealing molecular mechanisms regulating responses to DNA double-strand breaks." @default.
- W2012607520 created "2016-06-24" @default.
- W2012607520 creator A5005287620 @default.
- W2012607520 creator A5012431295 @default.
- W2012607520 creator A5018327095 @default.
- W2012607520 creator A5019310643 @default.
- W2012607520 creator A5024968631 @default.
- W2012607520 creator A5027784705 @default.
- W2012607520 creator A5042104290 @default.
- W2012607520 creator A5049992764 @default.
- W2012607520 creator A5059713279 @default.
- W2012607520 creator A5065867383 @default.
- W2012607520 creator A5088105104 @default.
- W2012607520 date "2014-02-03" @default.
- W2012607520 modified "2023-09-23" @default.
- W2012607520 title "ATP-driven Rad50 conformations regulate DNA tethering, end resection, and ATM checkpoint signaling" @default.
- W2012607520 cites W1575498014 @default.
- W2012607520 cites W1596997688 @default.
- W2012607520 cites W1938372995 @default.
- W2012607520 cites W1965379885 @default.
- W2012607520 cites W1967012607 @default.
- W2012607520 cites W1969008019 @default.
- W2012607520 cites W1970578083 @default.
- W2012607520 cites W1971294629 @default.
- W2012607520 cites W1971419576 @default.
- W2012607520 cites W1971793867 @default.
- W2012607520 cites W1973678001 @default.
- W2012607520 cites W1974093948 @default.
- W2012607520 cites W1975192924 @default.
- W2012607520 cites W1984084102 @default.
- W2012607520 cites W1984896911 @default.
- W2012607520 cites W1987469328 @default.
- W2012607520 cites W1987615467 @default.
- W2012607520 cites W1994954342 @default.
- W2012607520 cites W1995586409 @default.
- W2012607520 cites W2010233450 @default.
- W2012607520 cites W2019016428 @default.
- W2012607520 cites W2028921845 @default.
- W2012607520 cites W2031923605 @default.
- W2012607520 cites W2034117030 @default.
- W2012607520 cites W2035506170 @default.
- W2012607520 cites W2040838669 @default.
- W2012607520 cites W2041065032 @default.
- W2012607520 cites W2048533402 @default.
- W2012607520 cites W2049066045 @default.
- W2012607520 cites W2050735029 @default.
- W2012607520 cites W2059168612 @default.
- W2012607520 cites W2067060338 @default.
- W2012607520 cites W2068625350 @default.
- W2012607520 cites W2074351520 @default.
- W2012607520 cites W2082981258 @default.
- W2012607520 cites W2084089807 @default.
- W2012607520 cites W2086707417 @default.
- W2012607520 cites W2086932102 @default.
- W2012607520 cites W2087239831 @default.
- W2012607520 cites W2087430954 @default.
- W2012607520 cites W2098550464 @default.
- W2012607520 cites W2098813501 @default.
- W2012607520 cites W2100285961 @default.
- W2012607520 cites W2120486350 @default.
- W2012607520 cites W2121554894 @default.
- W2012607520 cites W2123909581 @default.
- W2012607520 cites W2124837740 @default.
- W2012607520 cites W2126492332 @default.
- W2012607520 cites W2130779427 @default.
- W2012607520 cites W2133993902 @default.
- W2012607520 cites W2134560191 @default.
- W2012607520 cites W2142654956 @default.
- W2012607520 cites W2148311403 @default.
- W2012607520 cites W2159490715 @default.
- W2012607520 cites W2161560609 @default.
- W2012607520 doi "https://doi.org/10.1002/embj.201386100" @default.
- W2012607520 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4818762" @default.
- W2012607520 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27037288" @default.
- W2012607520 hasPublicationYear "2014" @default.
- W2012607520 type Work @default.
- W2012607520 sameAs 2012607520 @default.
- W2012607520 citedByCount "127" @default.
- W2012607520 countsByYear W20126075202014 @default.
- W2012607520 countsByYear W20126075202015 @default.
- W2012607520 countsByYear W20126075202016 @default.
- W2012607520 countsByYear W20126075202017 @default.
- W2012607520 countsByYear W20126075202018 @default.
- W2012607520 countsByYear W20126075202019 @default.
- W2012607520 countsByYear W20126075202020 @default.
- W2012607520 countsByYear W20126075202021 @default.
- W2012607520 countsByYear W20126075202022 @default.
- W2012607520 countsByYear W20126075202023 @default.
- W2012607520 crossrefType "journal-article" @default.
- W2012607520 hasAuthorship W2012607520A5005287620 @default.
- W2012607520 hasAuthorship W2012607520A5012431295 @default.
- W2012607520 hasAuthorship W2012607520A5018327095 @default.
- W2012607520 hasAuthorship W2012607520A5019310643 @default.
- W2012607520 hasAuthorship W2012607520A5024968631 @default.
- W2012607520 hasAuthorship W2012607520A5027784705 @default.
- W2012607520 hasAuthorship W2012607520A5042104290 @default.
- W2012607520 hasAuthorship W2012607520A5049992764 @default.
- W2012607520 hasAuthorship W2012607520A5059713279 @default.