Replication stress, particularly in hard-to-replicate regions such as telomeres and centromeres, leads to the accumulation of replication intermediates that must be processed to ensure proper chromosome segregation. In this study, we identify a critical role for the interaction between RECQ4 and MUS81 in managing such stress. We show that RECQ4 physically interacts with MUS81, targeting it to specific DNA substrates and enhancing its endonuclease activity. Loss of this interaction, results in significant chromosomal segregation defects, including the accumulation of micronuclei, anaphase bridges, and ultrafine bridges (UFBs). Our data further demonstrate that the RECQ4-MUS81 interaction plays an important role in ALT-positive cells, where MUS81 foci primarily colocalise with telomeres, highlighting its role in telomere maintenance. We also observe that a mutation associated with Rothmund-Thomson syndrome, which produces a truncated RECQ4 unable to interact with MUS81, recapitulates these chromosome instability phenotypes. This underscores the importance of RECQ4-MUS81 in safeguarding genome integrity and suggests potential implications for human disease. Our findings demonstrate the RECQ4-MUS81 interaction as a key mechanism in alleviating replication stress at hard-to-replicate regions and highlight its relevance in pathological conditions such as RTS.

• MeSH
• chromozomální nestabilita MeSH
• DNA vazebné proteiny * metabolismus   genetika   MeSH
• helikasy RecQ * metabolismus   genetika   MeSH
• homeostáza telomer * MeSH
• lidé MeSH
• mutace MeSH
• replikace DNA MeSH
• Rothmundův-Thomsonův syndrom * genetika   metabolismus   MeSH
• segregace chromozomů MeSH
• telomery * metabolismus   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA vazebné proteiny * MeSH
• endonukleasy MeSH
• helikasy RecQ * MeSH
• MUS81 protein, human MeSH Prohlížeč
• RECQL4 protein, human MeSH Prohlížeč

N6-methyladenosine (m6A) and N6,2'-O-dimethyladenosine (m6Am) are two abundant modifications found in mRNAs and ncRNAs that can regulate multiple aspects of RNA biology. They function mainly by regulating interactions with specific RNA-binding proteins. Both modifications are linked to development, disease and stress response. To date, three methyltransferases and two demethylases have been identified that modify adenosines in mammalian mRNAs. Here, we present a comprehensive analysis of the interactomes of these enzymes. PCIF1 protein network comprises mostly factors involved in nascent RNA synthesis by RNA polymerase II, whereas ALKBH5 is closely linked with most aspects of pre-mRNA processing and mRNA export to the cytoplasm. METTL16 resides in subcellular compartments co-inhabited by several other RNA modifiers and processing factors. FTO interactome positions this demethylase at a crossroad between RNA transcription, RNA processing and DNA replication and repair. Altogether, these enzymes share limited spatial interactomes, pointing to specific molecular mechanisms of their regulation.

• MeSH
• adaptorové proteiny signální transdukční genetika   metabolismus   MeSH
• adenosin analogy a deriváty   metabolismus   MeSH
• alfa-ketoglutarát-dependentní dioxygenasa, AlkB homolog 5 genetika   metabolismus   MeSH
• anotace sekvence MeSH
• gen pro FTO genetika   metabolismus   MeSH
• genetická transkripce MeSH
• genová ontologie MeSH
• HEK293 buňky MeSH
• jaderné proteiny genetika   metabolismus   MeSH
• lidé MeSH
• mapování interakce mezi proteiny MeSH
• messenger RNA genetika   metabolismus   MeSH
• methyltransferasy genetika   metabolismus   MeSH
• N-demethylasy genetika   metabolismus   MeSH
• nekódující RNA genetika   metabolismus   MeSH
• oprava DNA MeSH
• protein - isoformy genetika   metabolismus   MeSH
• replikace DNA MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adaptorové proteiny signální transdukční MeSH
• adenosin MeSH
• alfa-ketoglutarát-dependentní dioxygenasa, AlkB homolog 5 MeSH
• ALKBH5 protein, human MeSH Prohlížeč
• FTO protein, human MeSH Prohlížeč
• gen pro FTO MeSH
• jaderné proteiny MeSH
• messenger RNA MeSH
• methyltransferasy MeSH
• METTL16 protein, human MeSH Prohlížeč
• N-demethylasy MeSH
• N-methyladenosine MeSH Prohlížeč
• N(6),N(6)-dimethyladenosine MeSH Prohlížeč
• nekódující RNA MeSH
• PCIF1 protein, human MeSH Prohlížeč
• protein - isoformy MeSH