Please use this identifier to cite or link to this item:
Title: RUNX Poly(ADP-Ribosyl)ation and BLM Interaction Facilitate the Fanconi Anemia Pathway of DNA Repair
Authors: Tay, L.S. 
Krishnan, V. 
Sankar, H. 
Chong, Y.L.
Chuang, L.S.H. 
Tan, T.Z. 
Kolinjivadi, A.M. 
Kappei, D. 
Ito, Y. 
Keywords: BLM
DNA repair
Fanconi anemia
interstrand crosslink repair
Issue Date: 2018
Publisher: Elsevier B.V.
Citation: Tay, 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.
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Abstract: The 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
Source Title: Cell Reports
ISSN: 22111247
DOI: 10.1016/j.celrep.2018.07.038
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1016_j_celrep_2018_07_038.pdf3.17 MBAdobe PDF



Google ScholarTM



This item is licensed under a Creative Commons License Creative Commons