Ask about this productRelated genes to: NHEJ1 antibody
- Gene:
- NHEJ1 NIH gene
- Name:
- non-homologous end joining factor 1
- Previous symbol:
- -
- Synonyms:
- Cernunnos, XLF, FLJ12610
- Chromosome:
- 2q35
- Locus Type:
- gene with protein product
- Date approved:
- 2006-03-30
- Date modifiied:
- 2019-04-23
Related products to: NHEJ1 antibody
Related articles to: NHEJ1 antibody
- Germline mutations play a pivotal role in evolution and are the primary cause of hereditary diseases in humans. Although interpopulation and interspecific variations in the mutation rate and spectrum are observed, their underlying genetic basis is still unclear. In this study, we explore the genetic regulation of germline mutation rates using one of the largest publicly available datasets derived from parent-offspring whole-genome sequencing. We first showed that germline mutation rates are strongly correlated between siblings, suggesting the influence of heritable factors. We then performed a genome-wide association study (GWAS), identifying 14 loci significantly associated with mutation rates, Notably, a lead single-nucleotide polymorphism (SNP) in the gene, critical for DNA repair, was linked to a 27% increase in maternal mutation rates and a significant shift toward A-to-T mutations only in females. This mutator allele is particularly prevalent in East Asian populations, where a similar shift in the A-to-T mutation spectrum has been observed. Evolutionary analysis suggests that this allele likely emerged in the common ancestor of humans and the genus. Furthermore, the genotype at the lead SNP position in species is also the same as the human mutator allele, supporting the potential role for this allele to explain the accelerated A-to-T mutations observed in the human- lineage. Together, these results indicate that genetic variants, particularly in DNA repair pathways, contribute to variation in mutation rates and spectra across individuals and populations, with a notable sex-specific effect. - Source: PubMed
Publication date: 2026/07/31
Wu KunNan JiuhongLiu Haoxuan - Sex-specific control of genome editing remains a significant challenge in birds. Chickens exhibit a ZW sex-determination system in which the Z and W chromosomes encode genes essential for sex differentiation and germline development, providing a rationale for sex-linked genome engineering. In this study, we established the sex chromosome-linked knock-in system for Cas9 in chicken primordial germ cells (PGCs). Donor constructs carrying Cas9-GFP were engineered to integrate into either the Z chromosome (DMRT1-DMRT3 intergenic region) or the W chromosome (5' region of HINTW locus). The targeting strategy was validated in DF-1 fibroblasts and PGCs, where site-specific integration was confirmed by junction PCR and sequencing. Functionality of the integrated Cas9 was verified by targeting two different loci, demonstrating efficient genome cleavage at NHEJ1 loci and indel-associated loss of GFP fluorescence following GFP targeting. The knock-in PGCs expressed Cas9 protein while retaining germ cell markers and migration capacity, demonstrating preservation of germline identity. Collectively, our findings establish a sex chromosome-linked Cas9 knock-in system in chicken PGCs and demonstrate that these sites support stable Cas9 expression without compromising germline characteristics, thereby providing a practical foundation for controlled, sex-specific genome engineering in avian research. - Source: PubMed
Publication date: 2026/07/02
Jung Kyung MinMony Sabrina IslamChen Paula RLee KihoLee Hong Jo - - Source: PubMed
Publication date: 2026/05/15
Alhaider AlanoudAlmutairi MansourAlomari AbdulazizAltuwaijri AlwaleedAlmarshoud GhaidaAlakrash Lamia - The DNA damage response (DDR) is a complex network of cellular pathways that ensures the faithful maintenance of our genomes upon a wide array of genomic insults. To elucidate the functional architecture of this network, we conducted unbiased genetic interaction screens using the Cas12a genome editor to disrupt 233 DDR genes frequently mutated in cancer and other genetic diseases, either individually or in pairwise combinations. This approach enabled us to assess the phenotypic effects induced by the disruption of >27,000 DDR gene pair combinations under unperturbed cell growth conditions. From this analysis, we identified over 750 high-confidence positive (buffering) or negative (synthetic lethal/sick) gene-gene interactions, along with multiple connections between previously unlinked DDR pathways and modules, allowing us to define novel aspects of the cellular response to spontaneous, DNA replication-associated DNA damage. Among the identified genetic interactions, we uncovered profound synthetic lethal interactions between genes encoding 1) the translesion polymerase REV1-Pol ζ complex and the MCM8-MCM9-HROB DNA helicase complex; 2) Fanconi Anemia (FA) proteins and the mitotic DNA repair factors GEN1, CIP2A, and RHINO; and 3) the DNA translocase SMARCAL1 and components of the FANCM complex, suggesting novel opportunities for targeted therapies in tumors carrying mutations in these genes. Additionally, we identified robust suppressor interactions between the gene encoding the nuclease APOLLO and the core non-homologous end joining (NHEJ) genes , , and , suggesting that NHEJ impairs the fitness of APOLLO-deficient cells. This work provides a functional map of the DDR network and demonstrates the power of Cas12a-based screens for identifying synthetic lethal and buffering interactions with therapeutic potential. - Source: PubMed
Publication date: 2026/06/08
Hayward Samuel BVaitsiankova AlinaLama-Diaz TomasChou JuihsuanTaglialatela AngeloHuang Jen-WeiWijesekarahanthi YodharaudshaniHeyza Joshua RLeuzzi GiuseppeChen ChuanyuanWong NancyLhakhang TenzinFu XiBuendia Alejandro LGheorghe VeronicaAnvar Nazanin EsmaeiliSchmidt Jens CNussenzweig AndreRabadan RaulCostanzo VincenzoGuérois RaphaëlHart TraverCiccia Alberto - Inborn errors of immunity (IEIs) are rare diseases that affect the immune system. Variants in over 500 genes have been identified as causative of 555 IEIs, with clinical phenotypes that can be heterogeneous within the same gene or even within the same variant. Therefore, these challenges make it difficult to determine the cause of IEI in individuals with immune disorders and to link clinical phenotypes to the precise genetic damage. An incorrect diagnosis can miss approximately 25% of IEI patients with overlapping initial manifestations. Accurate diagnosis and timely treatment are essential to improving quality of life and prolonging the lives of patients, as these patients often suffer from severe, life-threatening infections if left untreated. - Source: PubMed
Publication date: 2026/05/28
Kim Lien Nguyen ThiVan Tung NguyenMinh Huong Le ThiVan Anh Nguyen ThiPhuong Mai Nguyen ThiDien Tran MinhHien Nguyen ThanhTao Nguyen ThienHoang Nguyen Huy