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Fork Cleavage-Religation Cycle and Active Transcription Mediate Replication Restart after Fork Stalling at Co-transcriptional R-Loops

N. Chappidi, Z. Nascakova, B. Boleslavska, R. Zellweger, E. Isik, M. Andrs, S. Menon, J. Dobrovolna, C. Balbo Pogliano, J. Matos, A. Porro, M. Lopes, P. Janscak,

. 2020 ; 77 (3) : 528-541.e8. [pub] 20191120

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20023178
E-zdroje Online Plný text

NLK Cell Press Free Archives od 1997-12-01 do Před 1 rokem
Free Medical Journals od 1997 do Před 1 rokem
Free Medical Journals od 1997 do Před 1 rokem
Open Access Digital Library od 1997-12-01
Elsevier Open Access Journals od 1997-12-01 do 2023-06-15
Elsevier Open Archive Journals od 1997-12-01 do Před 1 rokem

Formation of co-transcriptional R-loops underlies replication fork stalling upon head-on transcription-replication encounters. Here, we demonstrate that RAD51-dependent replication fork reversal induced by R-loops is followed by the restart of semiconservative DNA replication mediated by RECQ1 and RECQ5 helicases, MUS81/EME1 endonuclease, RAD52 strand-annealing factor, the DNA ligase IV (LIG4)/XRCC4 complex, and the non-catalytic subunit of DNA polymerase δ, POLD3. RECQ5 disrupts RAD51 filaments assembled on stalled forks after RECQ1-mediated reverse branch migration, preventing a new round of fork reversal and facilitating fork cleavage by MUS81/EME1. MUS81-dependent DNA breaks accumulate in cells lacking RAD52 or LIG4 upon induction of R-loop formation, suggesting that RAD52 acts in concert with LIG4/XRCC4 to catalyze fork religation, thereby mediating replication restart. The resumption of DNA synthesis after R-loop-associated fork stalling also requires active transcription, the restoration of which depends on MUS81, RAD52, LIG4, and the transcription elongation factor ELL. These findings provide mechanistic insights into transcription-replication conflict resolution.

Citace poskytuje Crossref.org

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