NBS1-CtIP-Mediated DNA End Resection Regulates cGAS Binding to Micronuclei
Abdisalaam, S.; Mukherjee, S.; Bhattacharya, S.; Sinha, D.; Kumari, S.; Sadek, H. A.; Ortega, J.; Li, G.-M.; Aroumougame, A.
Show abstract
Cyclic GMP-AMP synthase (cGAS), an important component of immune signaling, is hyperactivated in cells defective for DNA damage response (DDR) signaling. However, a direct role for DDR factors in the regulation of cGAS functions is mostly unknown. Here, we provide novel evidence that Nijmegen breakage syndrome 1 (NBS1) protein, a well-studied DNA double-strand break (DSB) sensor, in coordination with ATM, a protein kinase, and CtBP-interacting protein (CtIP), a DNA end resection factor, functions as an upstream regulator of cGAS binding to micronuclei. Upon NBS1 binding to micronuclei via its fork-head-associated domain, it recruits ATM and CtIP via its N- and C-terminal domains, respectively. Subsequently, ATM stabilizes NBS1s interaction with micronuclei, and CtIP converts DSB ends into single-strand DNA ends, and these two key events preclude cGAS from binding to micronuclei. Notably, we show that purified cGAS cannot form a complex with DNA substrates that mimic resected DNA ends in vitro. Thus, NBS1 together with its binding partners modify the chromatin architecture of the micronuclei and that plays a critical role in cGASs binding to micronuclei.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Nucleolar reorganization after cellular stress is orchestrated by SMN shuttling between nuclear compartments 96%
- The RING Finger E3 Ligase RNF25 Protects DNA Replication Forks Independently of its Canonical Roles in Ubiquitin Signaling 96%
- The CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis 96%
Similar papers in this journal
- Topological stress triggers persistent DNA lesions in ribosomal DNA with ensuing formation of PML-nucleolar compartment 97%
- Systematic analysis of the molecular and biophysical properties of key DNA damage response factors 95%
- Image-based identification and isolation of micronucleated cells to dissect cellular consequences 95%
Similar papers in this journal
- BRD4 Prevents R-Loop Formation and Transcription-Replication Conflicts by Ensuring Efficient Transcription Elongation 95%
- Topoisomerase 1 dependent R-loop deficiency drives accelerated replication and genomic instability 95%
- Temporal dynamics of base excision / single-strand break repair protein complex assembly and disassembly are modulated by the PARP1/NAD+/SIRT6 axis 95%
Similar papers in this journal
- A novel role for the peptidyl-prolyl cis-trans isomerase Cyclophilin A in DNA-repair following replication fork stalling via the MRE11-RAD50-NBS1 complex. 94%
- Human PC4 supports telomere stability and viability in cells utilizing the alternative lengthening of telomeres mechanism 94%
- Combination of AID2 and BromoTag expands the utility of degron-based protein knockdowns 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.