CHK2 Regulates MUS81-EME2 Function in Response to Replication Stress and BRCA2 Deficiency
Malacaria, E.; Palma, A.; Rinalducci, S.; Franchitto, A.; Pichierri, P.
Show abstract
MUS81 is a structure-specific endonuclease that processes DNA intermediates in mitosis and in S-phase following replication stress. MUS81 is crucial to cleave deprotected reversed forks in BRCA2-deficient cells. However, how MUS81 is regulated during replication stress in human cells remains unknown. Our study reveals that CHK2 binds the MUS81-EME2 complex and positively regulates formation of DSBs upon replication stress or in the absence of BRCA2. The association with MUS81 occurs through the FHA domain of CHK2 and is disabled by the I157T mutation but not by the R117A mutation. The CHK2-MUS81 complex forms downstream fork reversal and degradation, and phosphorylation of MUS81 at CHK2-targeted sites is crucial to introduce DSBs at deprotected replication forks ensuring the replication fork recovery in BRCA2-deficient cells. Collectively, our work sheds light into the regulation of the MUS81 complex and identifies a novel function of the ATM-CHK2 axis in the response to deprotected replication forks in the absence of BRCA2.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- RIF1-ASF1-mediated high-order chromatin structure safeguards genome integrity 97%
- The Fanconi anemia core complex promotes CtIP-dependent end-resection to drive homologous recombination at DNA double-strand breaks 97%
- Timely lagging strand maturation relies on Ubp10-mediated PCNA dissociation from replicating chromatin 97%
Similar papers in this journal
Similar papers in this journal
- DROSHA, DICER and Damage-Induced long ncRNA control BMI1-dependent transcriptional repression at DNA double-strand break 96%
- BRD4 Prevents R-Loop Formation and Transcription-Replication Conflicts by Ensuring Efficient Transcription Elongation 96%
- The FANCD2-FANCI heterodimer coordinates chromatin openness and cell cycle progression throughout DNA double-strand break repair. 95%
Similar papers in this journal
- Human HMGN1 and HMGN2 are not required for transcription-coupled DNA repair 95%
- Sequential deregulation of histone marks, chromatin accessibility and gene expression in response to PROTAC-induced degradation of ASH2L 95%
- Alternative catalytic residues in the active site of Esco acetyltransferases 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.