Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.celrep.2018.07.038
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dc.titleRUNX Poly(ADP-Ribosyl)ation and BLM Interaction Facilitate the Fanconi Anemia Pathway of DNA Repair
dc.contributor.authorTay, L.S.
dc.contributor.authorKrishnan, V.
dc.contributor.authorSankar, H.
dc.contributor.authorChong, Y.L.
dc.contributor.authorChuang, L.S.H.
dc.contributor.authorTan, T.Z.
dc.contributor.authorKolinjivadi, A.M.
dc.contributor.authorKappei, D.
dc.contributor.authorIto, Y.
dc.date.accessioned2021-12-16T07:55:25Z
dc.date.available2021-12-16T07:55:25Z
dc.date.issued2018
dc.identifier.citationTay, L.S., Krishnan, V., Sankar, H., Chong, Y.L., Chuang, L.S.H., Tan, T.Z., Kolinjivadi, A.M., Kappei, D., Ito, Y. (2018). RUNX Poly(ADP-Ribosyl)ation and BLM Interaction Facilitate the Fanconi Anemia Pathway of DNA Repair. Cell Reports 24 (7) : 1747-1755. ScholarBank@NUS Repository. https://doi.org/10.1016/j.celrep.2018.07.038
dc.identifier.issn22111247
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/210869
dc.description.abstractThe Fanconi anemia (FA) pathway is a pivotal genome maintenance network that orchestrates the repair of DNA interstrand crosslinks (ICLs). The tumor suppressors RUNX1 and RUNX3 were shown to regulate the FA pathway independent of their canonical transcription activities, by controlling the DNA damage-dependent chromatin association of FANCD2. Here, in further biochemical characterization, we demonstrate that RUNX3 is modified by PARP-dependent poly(ADP-ribosyl)ation (PARylation), which in turn allows RUNX binding to DNA repair structures lacking transcription-related RUNX consensus motifs. SILAC-based mass spectrometric analysis revealed significant association of RUNX3 with core DNA repair complexes, including PARP1, even in unstressed cells. After DNA damage, the increased interaction between RUNX3 and BLM facilitates efficient FANCD2 chromatin localization. RUNX-Walker motif mutations from breast cancers are impaired for DNA damage-inducible PARylation, unveiling a potential mechanism for FA pathway inactivation in cancers. Our results reinforce the emerging paradigm that RUNX proteins are tumor suppressors with genome gatekeeper function. Tay et al. demonstrate that the tumor suppressor genes RUNX1 and RUNX3 have an important regulatory role in the genome maintenance pathway controlled by FANCD2. DNA damage induces PARP-dependent PARylation of RUNX proteins, leading to their interaction with BLM to control the loading of FANCD2 on DNA damage sites. © 2018 The Authors
dc.publisherElsevier B.V.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScopus OA2018
dc.subjectBLM
dc.subjectDNA repair
dc.subjectFANCD2
dc.subjectFanconi anemia
dc.subjectinterstrand crosslink repair
dc.subjectPARP1
dc.subjectpoly(ADP-ribosyl)ation
dc.subjectRUNX1
dc.subjectRUNX3
dc.subjectSILAC
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentDEPT OF MEDICINE
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1016/j.celrep.2018.07.038
dc.description.sourcetitleCell Reports
dc.description.volume24
dc.description.issue7
dc.description.page1747-1755
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