Ask about this productRelated genes to: MLH1 antibody
- Gene:
- MLH1 NIH gene
- Name:
- mutL homolog 1
- Previous symbol:
- COCA2
- Synonyms:
- HNPCC, FCC2, HNPCC2
- Chromosome:
- 3p22.2
- Locus Type:
- gene with protein product
- Date approved:
- 1993-11-24
- Date modifiied:
- 2019-04-23
Related products to: MLH1 antibody
Related articles to: MLH1 antibody
- TRDMT1 is an RNA methyltransferase that catalyzes 5-methylcytosine (m5C) formation in R-loops to promote transcription-coupled homologous recombination (TC-HR). Although TRDMT1 inhibition selectively kills BRCA1-deficient cancer cells, broader cancer dependencies on TRDMT1 remain unclear. Here, a TRDMT1 inhibitor (TRDMT1i) sensitivity screen across a large panel of cancer cell lines identifies loss of MLH1 or PMS2, two components of the MutLα mismatch repair (MMR) complex frequently inactivated in tumors, as key determinants of TRDMT1 dependency. In contrast, MutLβ and MutSα/β are dispensable for TRDMT1i resistance, revealing a unique MMR-independent function of MutLα. Mechanistically, TRDMT1 and MutLα independently recognize DNA-RNA hybrids and cooperatively suppress co-transcriptional R-loops genome-wide in undamaged cells, with m5C directing pathway choice. Furthermore, MutLα suppresses R-loops through its ATPase and endonuclease activities and through recruitment of EXO1. Combined loss of TRDMT1 and MLH1 causes extensive R-loop accumulation and transcription replication conflicts (TRCs), impairing replication fork progression, inducing DNA damage, and driving apoptosis-mediated synthetic lethality. Importantly, TRDMT1i suppresses growth of MLH1-deficient tumors by inducing TRCs in vivo, suggesting a potential therapeutic strategy for targeting MutLα-deficient tumors. These studies not only expand our understanding of cancer dependency on TRDMT1, but also identify a promising strategy to exploit TRCs in cancer therapy. - Source: PubMed
Publication date: 2026/08/10
Ghosh ArijitRan XiaojuanZhang FengqiGao BoyaXu YuPhoon Lai-YeeLong MelissaWang MingchaoAnanthapadmanabhan VarshaKawale AjinkyaShah YugManzano-Winkler BrendaOtt Christopher JZou LeeLan Li - There is lack of data pertaining to Lynch syndrome presenting as endometrial cancer in Quebec. We evaluated real-world follow-up of mismatch repair-deficient (dMMR) endometrial cancers screened through universal immunohistochemistry at a tertiary center in Québec. Among 222 dMMR tumors, MLH1/PMS2 loss predominated. Seventy-four patients with methylation-negative tumors were eligible for Lynch syndrome evaluation; 73 (98.6%) were referred, and 57 completed germline testing. Pathogenic germline variants were identified in 54.4%. These findings demonstrate high downstream testing uptake and a substantial diagnostic yield, underscoring the importance of systematic linkage from tumor screening to genetic assessment to optimize Lynch syndrome detection. - Source: PubMed
Publication date: 2026/09/07
Eiley EmilyLevin GabrielGilbert LucyRibeiro ReitanLeung AnnieBernard LaurenceSkolnik DerekGanesu BaviZeng Xing - To characterize clinicopathologic features of microsatellite instability-high (MSI-high) gynecologic malignancies in Japan and evaluate outcomes of pembrolizumab in MSI-high endometrial cancer, including an exploratory assessment of promoter methylation and obesity. - Source: PubMed
Publication date: 2026/08/24
Kashima YokoMurakami KosukeOtani TomoyukiYoriki KaoriKaneda MichikoFujiwara SatoeKatsuda TakahiroNagano HiroakiHayasaki YouKai KentaroArakawa AtsushiMochizuki AyakoHirashima YasuyukiIwahashi NaoyukiMotohashi TakashiYoshioka EmiIto KimihikoNakai HidekatsuMatsumura Noriomi - Cancer of unknown primary (CUP) is aggressive, with limited options and poor prognosis. Mismatch repair-deficient (dMMR) CUP is rare, and reports of its response to immunotherapy are scarce. - Source: PubMed
Publication date: 2026/08/20
Turker MehmetDusgun AlpayTurker AliSelvi SeherAlisan IrfanBuyuksimsek Mahmut - Indigenous chickens play a critical role in food security and climate resilience in smallholder systems, yet their genomic diversity and adaptive potential remain insufficiently characterised. This study employed low-pass whole-genome sequencing (LP-WGS; 0.2-1.99×) to investigate genomic diversity, population structure, inbreeding and candidate environment-associated genomic variation in 33 chickens from highland, midland, and lowland agroecologies in the Tigray region of northern Ethiopia. After imputation and stringent filtering, 23.4 million high-confidence SNPs were retained, including ~ 17% novel variants, indicating substantial uncharacterised genetic diversity in these populations. SNP density (13.8 ± 8.6 SNPs/kb) was comparable to values reported from high-coverage Ethiopian chicken datasets, demonstrating the suitability of LP-WGS for population genomics in resource-limited settings. Marked differences in genomic diversity were observed among ecotypes: midland chickens showed the highest nucleotide diversity (π = 0.00267), followed by lowland (π = 0.00233), whereas highland chickens showed the lowest diversity (π = 0.00203) and elevated genomic inbreeding (F and F ≈ 0.18). Population structure analyses revealed clear genetic separation among ecotypes. PCA (13.91% variation explained) distinguished lowland chickens along PC1 and separated highland from midland along PC2, while ADMIXTURE and F patterns supported three major ancestral genomic backgrounds. Functional annotation of private missense variants uncovered distinct adaptive signatures reflecting the contrasting agroecological conditions. Highland chickens showed enrichment of candidate genes potentially involved in physiological processes relevant to high-altitude environments, including cold response, angiogenesis, cardiovascular regulation and metabolic homeostasis (eg., PARP1, ACOX2, ITGB3, EDNRB, SOX8, and SOX10). Midland chickens exhibited candidate signals of selection in genes with known roles in innate antiviral immunity, bacterial defence and inflammatory regulation (eg., BAK1, CLSTN1, CYSLTR1, CYSLTR2, CXCR7, GIPR, DSCAM, GDAP1, TLR3, TLR4, TLR7, IFIH1, ADORA1, EPHB1, and TMPRSS2). Lowland chickens displayed candidate variants associated with heat-stress response, DNA damage repair, oxidative balance and cardiovascular support under extreme temperatures (e.g., MLH1, BDKRB1, GPR19, FLT1, CCL18, TGM2, and RAMP3). Overall, the results indicate substantial genomic differentiation among ecotypes and suggest candidate environment-associated genetic divergence across Tigray's diverse agroecological zones. These populations may represent important reservoirs of adaptive genetic variation for climate-resilient poultry breeding, warranting further functional validation and conservation-oriented management. - Source: PubMed
Publication date: 2026/09/02
Gebru GebreslassieBelay GurjaZegeye TsadkanDessie TadelleBirhanie MinisterZenebe MulalemSalim BashirKatrina MorrisHanotte OlivierVallejo-Trujillo Adriana