Property Summary

NCBI Gene PubMed Count 56
PubMed Score 79.80
PubTator Score 40.19

Knowledge Summary

Patent

No data available

Expression

 GO Function (1)

 GWAS Trait (1)

Gene RIF (44)

PMID Text
27437582 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
26100018 The data suggest that XLF has multiple functions in DNA repair, and they offer potential explanations for the pleiotropic phenotypes associated with XLF deficiency.
25661488 Phosphorylation of XLF impairs non-homologous end-joining DNA repair.
25321468 PC4 protects esophageal squamous cell carcinoma cells from IR-induced death by enhancing the nonhomologous end joining-promoting activity of XLF.
24626809 Werner syndrome protein positively regulates XRCC4-like factor transcription.
24461734 Human XLF is a non-essential, but critical, classic non-homologous end-joining -repair factor.
23818183 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.
23620595 Data indicate that Ku70/Ku80 facilitates the cooperative binding of multiple XRCC4/Ligase IV (XL) and XLF molecules to DNA.
23442139 XRCC4 and XLF form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair. (Review)
23207905 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.
22312109 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.
22287571 Evidence for how XRCC4-XLF complexes robustly bridge DNA molecules.
22102241 Multiple truncations of the XLF and XRCC4 proteins were cocrystallized, but yielded low-resolution diffraction (~20 A)
21936820 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.
21775435 molecular mechanism for XLF-XRCC4 stimulation of DNA ligation.
21768349 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.
21665306 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.
21349273 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.
20844317 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.
20597108 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.
20558749 identified three amino acids (Arg(64), Leu(65), and Leu(115)) essential for the interaction with X4 and the proper function of Cernunnos
20522537 Observational study of gene-disease association. (HuGE Navigator)
19806195 a natural mutator variant of human DNA polymerase lambda promotes chromosomal instability by compromising NHEJ
19584075 Observational study of gene-disease association. (HuGE Navigator)
19420065 Recombinant Cernunnos protein restored gap filling and end joining of partially complementary overhangs, and stimulated joining of cohesive ends more than twentyfold.
19266077 Observational study of gene-disease association. (HuGE Navigator)
19223975 role of Cernunnos/XLF in repair of DSBs and maintenance of genomic stability under replication stress conditions
19103754 the heads and coiled-coil regions of Cernunnos and X4 are not interchangeable, and they suggest specific roles for each in NHEJ
18775323 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.
18644470 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.
18335491 REVIEW: Role and regulation of XLF
18270339 Observational study and meta-analysis of gene-disease association. (HuGE Navigator)
18158905 Mutational analysis of XLF and XRCC4 reveals a potential interaction interface, suggesting a mechanism for how XLF stimulates the ligation of mismatched ends.
18046455 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.
17720816 Data shows that an intact XRCC4/ligase IV complex is necessary for Cernunnos-XLF mobilization to damaged chromatin.
17504121 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.
17470781 Cernunnos/XRCC4-like factor promotes a mismatched end (MEnd) DNA ligase activity to facilitate joining and to preserve DNA sequence.
17317666 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
17191205 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.
16828027 DNA repair protein involved in lymphocyte activation and cell division.
16571728 Cernunnos physically interacts with the XRCC4 x DNA-ligase IV complex
16439205 Studies on the binding of XLF and its role in DNA repair.
16439205 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.
16439204 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.

AA Sequence

MEELEQGLLMQPWAWLQLAENSLLAKVFITKQGYALLVSDLQQVWHEQVDTSVVSQRAKELNKRLTAPPA      1 - 70
AFLCHLDNLLRPLLKDAAHPSEATFSCDCVADALILRVRSELSGLPFYWNFHCMLASPSLVSQHLIRPLM     71 - 140
GMSLALQCQVRELATLLHMKDLEIQDYQESGATLIRDRLKTEPFEENSFLEQFMIEKLPEACSIGDGKPF    141 - 210
VMNLQDLYMAVTTQEVQVGQKHQGAGDPHTSNSASLQGIDSQCVNQPEQLVSSAPTLSAPEKESTGTSGP    211 - 280
LQRPQLSKVKRKKPRGLFS                                                       281 - 299
//

Text Mined References (59)

PMID Year Title
27437582 2016 Sliding sleeves of XRCC4-XLF bridge DNA and connect fragments of broken DNA.
26100018 2015 XRCC4/XLF Interaction Is Variably Required for DNA Repair and Is Not Required for Ligase IV Stimulation.
25941166 2015 XLS (c9orf142) is a new component of mammalian DNA double-stranded break repair.
25670504 2015 Interactome analysis identifies a new paralogue of XRCC4 in non-homologous end joining DNA repair pathway.
25661488 2015 Akt-mediated phosphorylation of XLF impairs non-homologous end-joining DNA repair.
25574025 2015 DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair.
25429064 2015 Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
25321468 2014 Inhibition of human positive cofactor 4 radiosensitizes human esophageal squmaous cell carcinoma cells by suppressing XLF-mediated nonhomologous end joining.
24626809 2014 Werner syndrome protein positively regulates XRCC4-like factor transcription.
24461734 2014 A role for XLF in DNA repair and recombination in human somatic cells.
24095731 2013 TRF2 interaction with Ku heterotetramerization interface gives insight into c-NHEJ prevention at human telomeres.
23818183 2013 Brief report: a human induced pluripotent stem cell model of cernunnos deficiency reveals an important role for XLF in the survival of the primitive hematopoietic progenitors.
23620595 2013 Cooperative assembly of a protein-DNA filament for nonhomologous end joining.
23442139 2013 XRCC4 and XLF form long helical protein filaments suitable for DNA end protection and alignment to facilitate DNA double strand break repair.
23207905 2013 Cernunnos deficiency reduces thymocyte life span and alters the T cell repertoire in mice and humans.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22312109 2012 Cernunnos influences human immunoglobulin class switch recombination and may be associated with B cell lymphomagenesis.
22287571 2012 A human XRCC4-XLF complex bridges DNA.
22102241 2011 Crystallization and preliminary X-ray diffraction analysis of the human XRCC4-XLF complex.
21936820 2011 Non-homologous end-joining partners in a helical dance: structural studies of XLF-XRCC4 interactions.
21775435 2011 XRCC4 protein interactions with XRCC4-like factor (XLF) create an extended grooved scaffold for DNA ligation and double strand break repair.
21768349 2011 Structural characterization of filaments formed by human Xrcc4-Cernunnos/XLF complex involved in nonhomologous DNA end-joining.
21665306 2011 In tumor cells regulation of DNA double strand break repair through EGF receptor involves both NHEJ and HR and is independent of p53 and K-Ras status.
21349273 2011 Functional significance of the interaction with Ku in DNA double-strand break recognition of XLF.
20844317 2010 ATM-independent, high-fidelity nonhomologous end joining predominates in human embryonic stem cells.
20597108 2010 Clinical variability and novel mutations in the NHEJ1 gene in patients with a Nijmegen breakage syndrome-like phenotype.
20558749 2010 Delineation of the Xrcc4-interacting region in the globular head domain of cernunnos/XLF.
20522537 2010 Variation within DNA repair pathway genes and risk of multiple sclerosis.
20383123 2010 Ku is a 5'-dRP/AP lyase that excises nucleotide damage near broken ends.
20189936 2010 A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci.
19806195 2009 Characterization of a natural mutator variant of human DNA polymerase lambda which promotes chromosomal instability by compromising NHEJ.
19584075 2009 Novel susceptibility loci for second primary tumors/recurrence in head and neck cancer patients: large-scale evaluation of genetic variants.
19420065 2009 Requirement for XLF/Cernunnos in alignment-based gap filling by DNA polymerases lambda and mu for nonhomologous end joining in human whole-cell extracts.
19266077 2009 Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the northern Finland birth cohort 1966.
19223975 2009 Impaired replication stress response in cells from immunodeficiency patients carrying Cernunnos/XLF mutations.
19103754 2009 The C-terminal domain of Cernunnos/XLF is dispensable for DNA repair in vivo.
18775323 2008 Lymphocyte-specific compensation for XLF/cernunnos end-joining functions in V(D)J recombination.
18644470 2008 DNA-PK and ATM phosphorylation sites in XLF/Cernunnos are not required for repair of DNA double strand breaks.
18391952 2008 Genome-wide association analysis identifies 20 loci that influence adult height.
18335491 2008 Role and regulation of human XRCC4-like factor/cernunnos.
18270339 2008 Comprehensive analysis of DNA repair gene variants and risk of meningioma.
18158905 2007 Crystal structure of human XLF: a twist in nonhomologous DNA end-joining.
18064046 2008 Ku recruits XLF to DNA double-strand breaks.
18046455 2008 Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ.
17720816 2007 Interplay between Cernunnos-XLF and nonhomologous end-joining proteins at DNA ends in the cell.
17504121 2007 Non-homologous DNA end joining in anticancer therapy.
17470781 2007 Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA ends.
17317666 2007 Length-dependent binding of human XLF to DNA and stimulation of XRCC4.DNA ligase IV activity.
17191205 2007 Truncation of NHEJ1 in a patient with polymicrogyria.
16828027 [Cernunnos, a novel DNA repair factor essential for the immune system].
16571728 2006 Cernunnos interacts with the XRCC4 x DNA-ligase IV complex and is homologous to the yeast nonhomologous end-joining factor Nej1.
16439205 2006 XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining.
16439204 2006 Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12604777 2003 Nonhomologous end joining and V(D)J recombination require an additional factor.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.