Recombinant Human Non-homologous end-joining factor 1 (NHEJ1)

1. this study shows loss of NHEJ1 protein due to a novel splice site mutation in a family presenting with combined immunodeficiency, microcephaly, and growth retardation PMID: 28741180
2. Phospho-blocking and -mimicking mutations impact both the stability and DNA bridging capacity of XRCC4/XLF complexes, but without affecting their ability to stimulate LIG4 activity. Implicit in this finding is that phosphorylation may regulate DNA bridging by XRCC4/XLF filaments. PMID: 28500754
3. Chemotherapy-induced overexpression of XLF and XLF-mediated enhancements in NHEJ activity contribute to chemoresistance in hepatocellular carcinoma (HCC) cells and patients with HCC. Targeting XLF to modulate DSB repair could enhance drug sensitivity and may be a therapeutically useful addition to conventional therapy PMID: 28526069
4. Although PAXX-deficient cells lack c-NHEJ phenotypes, PAXX forms a stable ternary complex with Ku bound to DNA. Thus, PAXX plays an accessory role during c-NHEJ that is largely overlapped by XLF's function. PMID: 27705800
5. The role of XLF in NHEJ is summarized. PMID: 28846869
6. XLF has an important role during V(D)J recombination. PMID: 27281794
7. using dual- and quadruple-trap optical tweezers combined with fluorescence microscopy, we show how human XRCC4, XLF and XRCC4-XLF complexes interact with DNA in real time PMID: 27437582
8. The data suggest that XLF has multiple functions in DNA repair, and they offer potential explanations for the pleiotropic phenotypes associated with XLF deficiency. PMID: 26100018
9. PC4 protects esophageal squamous cell carcinoma cells from IR-induced death by enhancing the nonhomologous end joining-promoting activity of XLF. PMID: 25321468
10. Phosphorylation of XLF impairs non-homologous end-joining DNA repair. PMID: 25661488
11. Werner syndrome protein positively regulates XRCC4-like factor transcription. PMID: 24626809
12. Human XLF is a non-essential, but critical, classic non-homologous end-joining -repair factor. PMID: 24461734
13. An induced pluripotent stem cell (iPSC) model of XLF deficiency, which accurately replicates the double-strand break repair deficiency observed in XLF syndrome patients, is reported. PMID: 23818183
14. Data indicate that Ku70/Ku80 facilitates the cooperative binding of multiple XRCC4/Ligase IV (XL) and XLF molecules to DNA. PMID: 23620595
15. XRCC4 and XLF form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair. (Review) PMID: 23442139
16. Cernunnos deficiency results in chronic activation of the DNA damage response, P53-driven upregulation of proapoptotic factors, leading to decreased thymocyte viability and a qualitative alteration of the T cell repertoire in both humans and mice. PMID: 23207905
17. Regulation of Double Strand Break repair by EGFR involves both the NHEJ and HR pathway, and appears to occur in most tumor cell lines regardless of p53 and K-Ras mutation status. PMID: 21665306
18. Evidence for how XRCC4-XLF complexes robustly bridge DNA molecules. PMID: 22287571
19. A suggested link between defects in the Cernunnos-dependent nonhomologous end-joining pathway and aberrant class switch recombination or switch translocations during the development of B cell malignancies. PMID: 22312109
20. Multiple truncations of the XLF and XRCC4 proteins were cocrystallized, but yielded low-resolution diffraction (~20 A) PMID: 22102241
21. Data show that XLF and XRCC4 dimers interact through their head domains and form an alternating left-handed helical structure with polypeptide coiled coils and pseudo-dyads of individual XLF and XRCC4 dimers at right angles to the helical axis. PMID: 21936820
22. molecular mechanism for XLF-XRCC4 stimulation of DNA ligation. PMID: 21775435
23. X-ray structure reveals a filament arrangement for XRCC4(1-157) and Cernunnos(1-224) homodimers mediated by repeated interactions through their N-terminal head domains. PMID: 21768349
24. Data show that the heterodimeric domain of Ku was sufficient for the recruitment of XLF to DSBs and for the interaction of Ku with XLF. PMID: 21349273
25. NHEJ in human embryonic stem cells is largely independent of ATM, DNA-PKcs, and PARP but dependent on XRCC4 with repair fidelity several-fold greater than in astrocytes. PMID: 20844317
26. Patients with NBS-like phenotypes may have mutations in the NHEJ1 gene including multiexon deletions, and show that considerable clinical variability could be observed even within the same family. PMID: 20597108
27. identified three amino acids (Arg(64), Leu(65), and Leu(115)) essential for the interaction with X4 and the proper function of Cernunnos PMID: 20558749
28. a natural mutator variant of human DNA polymerase lambda promotes chromosomal instability by compromising NHEJ PMID: 19806195
29. Cernunnos-XLF is a new Non-homologous End Joining pathway protein, which if mutated results in several conditions -immunodeficiency and developmental anomalies and other conditions, which likely result from inability to repair spontaneous DNA damage. PMID: 16439204
30. Studies on the binding of XLF and its role in DNA repair. PMID: 16439205
31. Cernunnos physically interacts with the XRCC4 x DNA-ligase IV complex PMID: 16571728
32. DNA repair protein involved in lymphocyte activation and cell division. PMID: 16828027
33. Results show that a truncated transcript of NHEJ1 is expressed in the polymicrogyric patient cells, suggesting a potential dominant negative effect possibly leading to a different phenotype. PMID: 17191205
34. mutant protein retained its ability to stimulate XRCC4.DNA ligase IV but failed to translocate to the nucleus, and this appears to be the basis for the non-homologous DNA end joining defect in this patient PMID: 17317666
35. Cernunnos/XRCC4-like factor promotes a mismatched end (MEnd) DNA ligase activity to facilitate joining and to preserve DNA sequence. PMID: 17470781
36. Review focuses on the proteins involved in the NHEJ pathway, the major pathway for repair of DNA double-strand breaks, which can become molecular targets in the treatment of cancer. PMID: 17504121
37. Data shows that an intact XRCC4/ligase IV complex is necessary for Cernunnos-XLF mobilization to damaged chromatin. PMID: 17720816
38. The XLF dimer adopts a similar overall structure to that of the XRCC4 dimer, supporting the contention that these two factors are related in function and have arisen from a common evolutionary ancestor. PMID: 18046455
39. Mutational analysis of XLF and XRCC4 reveals a potential interaction interface, suggesting a mechanism for how XLF stimulates the ligation of mismatched ends. PMID: 18158905
40. REVIEW: Role and regulation of XLF PMID: 18335491
41. The major phosphorylation sites in XLF, serine 245 is phosphorylated by DNA-PK, while serine 251 is phosphorylated by Ataxia-Telangiectasia Mutated (ATM), in vivo. PMID: 18644470
42. Results implicate XLF as a C-NHEJ factor but also indicate that developing mouse lymphocytes harbor cell-type-specific factors/pathways that compensate for the absence of XLF function during V(D)J recombination. PMID: 18775323
43. the heads and coiled-coil regions of Cernunnos and X4 are not interchangeable, and they suggest specific roles for each in NHEJ PMID: 19103754
44. role of Cernunnos/XLF in repair of DSBs and maintenance of genomic stability under replication stress conditions PMID: 19223975
45. Recombinant Cernunnos protein restored gap filling and end joining of partially complementary overhangs, and stimulated joining of cohesive ends more than twentyfold. PMID: 19420065
46. The XLF-encoded protein (XRRC4 like factor, FLJ12610) is involved in DNA double-strand break repair via nonhomologous end-joining and associates with the Ligase IV-XRCC4 complex. XLF is mutated in a number of radiosensitive and immuno-deficient patients. PMID: 16439205

Show More

Hide All

HGNC: 25737

OMIM: 611290

KEGG: hsa:79840

STRING: 9606.ENSP00000349313

UniGene: Hs.225988