Ask about this productRelated genes to: MUS81 Blocking Peptide
- Gene:
- MUS81 NIH gene
- Name:
- MUS81 structure-specific endonuclease subunit
- Previous symbol:
- -
- Synonyms:
- FLJ44872, SLX3
- Chromosome:
- 11q13
- Locus Type:
- gene with protein product
- Date approved:
- 2004-01-27
- Date modifiied:
- 2014-11-19
Related products to: MUS81 Blocking Peptide
Related articles to: MUS81 Blocking Peptide
- Crossover (CO) formation between homologous chromosomes is essential for genetic diversity and accurate meiotic chromosome segregation. This process involves two key steps: the designation of a subset of meiotic double-strand breaks to CO-designated sites and subsequent CO resolution by Holliday junction (HJ) resolvase. However, how these steps are functionally coupled remains elusive. Here, we showed that COSA-1, essential for CO designation, directly interacts with the SLX-4 scaffold protein, which organizes the SLX-1, XPF-1, and MUS-81 HJ resolvases. Disrupting this interaction results in persistent unrepaired recombination intermediates and defective CO formation. Notably, these defects can be largely rescued by the artificial tethering of SLX-4 to the CO designation proteins. We further demonstrate that COSA-1 promotes assembly of the SLX-4 resolvase complex and provide evidence that this mechanism coupling CO designation with resolution is evolutionarily conserved. Together, our findings support a model in which CO designation proteins ensure accurate CO formation by directly recruiting the resolution machinery. - Source: PubMed
Publication date: 2026/04/24
Liu GuotengYang YuejunNan WencongXiao TongxinGuo ZongyuZhang MeiyuWang YuchenWu XuezhenGartner AntonZhang HongtaoHong Ye - Activated oncogenes elicit genomic instability by inducing DNA replication stress. Here we show that replication fork reversal and chromosome mis-segregation induced by oncogenic RAS (HRASV12) or cyclin E1 overexpression are largely caused by co-transcriptional RNA:DNA hybrids (R-loops) formed during S-phase. Furthermore, we demonstrate that replication stress induced by HRASV12, but not cyclin E1, is driven by reactive oxygen species (ROS) in a manner dependent on the replisome-associated ROS sensor peroxiredoxin 2 (PRDX2) and is linked to PRDX2-mediated release of the fork acceleration factor TIMELESS from the replisome. Inhibition of fork reversal in cells overexpressing HRASV12 or cyclin E1 induces unrestrained DNA synthesis mediated by the MUS81 endonuclease and the primase-polymerase PRIMPOL, thereby promoting proper chromosome segregation in mitosis. These results establish PRIMPOL repriming as part of the MUS81-dependent replication restart mechanism that operates at sites of R-loop-mediated transcription-replication conflicts to maintain genomic stability. Furthermore, our data indicate that, despite their protective role during S-phase, persistent reversed forks impair chromosome segregation in mitosis, potentially leading to DNA breaks and chromosomal rearrangements. - Source: PubMed
Publication date: 2026/04/03
Oravetzova AnnaDvorakova MarketaMihai Anca-IrinaAndrs MartinSobol MargaritaZuev AntonShukla KaustubhBoleslavska BarboraRosano VinicioKönig ChristianeProkes JiriHanzlikova HanaMacurek LiborDobrovolna JanaJanscak Pavel - Maintaining genome integrity is essential, yet how DNA repair is balanced across life stages remains poorly understood. Here we uncover an epitranscriptomic mechanism in the fungal pathogen Fusarium graminearum that alleviates a trade-off between heat-stress adaptation and sexual reproduction. We show that FgMus81 acts independently of its nuclease activity and canonical partner FgMms4, and has dosage-dependent, stage-specific functions: restrained levels support meiosis, whereas elevated levels promote heat-stress survival. We identify a sexual stage-specific A-to-I RNA editing event that recodes FgMus81 (N420D) and tunes its abundance to meet meiotic demands without compromising stress resilience. Notably, both pre-editing and post-editing isoforms support meiotic interhomolog crossovers, but the post-editing isoform impairs mitotic recombination. Conservation of this editing across Sordariomycetes suggests evolutionary selection for stage-specific control. Together, these findings reveal an epitranscriptomic switch that partitions Mus81 functions across life stages and identify adaptive RNA editing as a regulator of homologous recombination in fungal pathogens. - Source: PubMed
Publication date: 2026/03/30
Wu MengchunLiu JunfengCao PeinaLiu MengqiaoFeng ChanjingWang QinhuJiang CongXu Jin-RongLiu Huiquan - Meiotic crossovers are generated from the repair of programmed DNA double-strand breaks (DSBs). In the budding yeast Saccharomyces cerevisiae and mammals, most crossovers are generated through the Class I pathway, involving the mismatch-repair related complex Msh4-Msh5, while a smaller fraction is produced by the Mms4-Mus81 endonuclease (Class II pathway). We present the first report on the genome-wide localization of the Mms4 protein during meiosis in S. cerevisiae. Surprisingly, Mms4 localization showed a trend towards weak DSB sites, unlike the localization of the Class I crossover protein -Msh5, which is biased towards strong DSB sites. This preference for weaker DSB hotspots was retained in a msh5∆ mutant, arguing against competitive models of Mms4 and Msh5 association on meiotic chromosomes. The chromosomal association of Mms4 does not require the formation of meiotic DNA breaks but is facilitated by chromosome axis assembly. These results suggest Mms4 is primarily associated with chromosomal axis regions positioned near recombination intermediates. Mms4 binding is also largely insensitive to heterozygosity, unlike Msh5, consistent with its independence from recombination for localization. Together, these findings support a model in which Mms4-Mus81 enhances the robustness of meiotic recombination with a trend towards binding DSB hotspots that are weaker or are located in regions with sequence divergence that may be processed less efficiently by the Class I pathway. - Source: PubMed
Publication date: 2026/03/30
Farnaz Amamah FarzlinJoshi SameerSarath PraseethaJogwar GirijaNishant Koodali T - Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is an acetyltransferase involved in sister chromatid cohesion. Here we demonstrated that ESCO2 has a new role in telomere maintenance through its binding with telomeric repeat-binding factor TRF1 and TRF2. Loss of ESCO2 induces aberrant DNA damage at telomeres and leads to dramatic telomere shortening. ESCO2 associates with several proteins involved in DNA replication and repair, including BLM, WRN, TopBP1, BRIP1, BRCA1, and MUS81. Moreover, we show that ESCO2 acts in epistasis with BLM in promoting telomere stability. Taken together, our data suggest that ESCO2 is required for the maintenance of telomere stability, presumably by coordinating multiple replication and repair factors to facilitate telomere replication and protection. - Source: PubMed
Publication date: 2026/03/13
Guo JiahuiJi JingjingLiu JinfengTang Mengfan