Overall, our data provide an unanticipated evidence of a close interaction between HP1 and NBS1 that is essential for genome stability and point up HP1α as a potential target to counteract chromosome instability in NBS patient cells.
In the NBS condition, the SPC showed a reduced activation (NBS = 3.97%; NBS + LS = 4.49%; LS = 4.48%; ND = 4.61% of the maximal voluntary contraction) compared to the other conditions.
Fibroblast-derived integration-free iPSC line ISRM-NBS1 from an 18-year-old Nijmegen Breakage Syndrome patient carrying the homozygous NBNc.657_661del5 mutation.
Recessive function-altering NBN variants typically cause Nijmegen breakage syndrome characterized by microcephaly, cancer predisposition, and immunodeficiency, none of which are evident in the patient.
Nijmegen breakage syndrome 1 (NBS1), as a key protein in the DNA double-strand breaks (DSBs) repair pathway, plays an important role in maintaining genomic stability.
Genetic analyses were performed and revealed a PDGFRB gene c.1681C>A missense heterozygous germline mutation, high PDGFRβ phosphokinase activity within the tumor and the heterozygous germline Slavic Nijmegen breakage syndrome657del5 mutation in the NBN gene.
Nijmegen breakage syndrome 1 (NBS1) is a component of MRE11/RAD50/NBS1 complex (MRN) that plays a critical role in the cellular response to DNA damage and maintenance of chromosomal integrity.
Our study demonstrates the utility of NBS-iPSCs as a screening platform for anti-oxidants capable of suppressing DNA damage and a cellular model for studying NBN de-regulation in cancer and microcephaly.
Furthermore, Parkin is found to physically interact with NBS1 (Nijmegen breakage syndrome 1), and to be required for optimal recruitment of NBS1 and DNA polymerase eta (Polη) to UV-induced damage sites.
We observed that the HCAR1 agonist dihydroxybenzoic acid (DHBA) up-regulated BRCA1 (breast cancer type 1 susceptibility protein) and NBS1 (Nijmegen breakage syndrome 1) expression in HeLa cells.
The vast majority of patients with Nijmegen Breakage Syndrome (NBS) are of Slavic origin and carry a deleterious deletion (c.657del5; rs587776650) in the NBN gene on chromosome 8q21.
We used here antisense oligonucleotides to enforce alternative splicing in NBS patient cells and efficiently generate the same internally deleted p80-nibrin protein.
In human NBS1, mutations result truncation of the N-terminus region, which contains a forkhead-associated (FHA) domain, cause Nijmegen breakage syndrome.
The prognostic impact of high Nijmegen breakage syndrome (NBS1) gene expression in ERG-negative prostate cancers lacking PTEN deletion is driven by KPNA2 expression.
Since some of the newly identified interactors of the p26 and p70 fragments have not been found to interact with the full-length NBN, these interactions may somehow contribute to the key biological phenomena underpinning NBS.
To verify whether truncated nibrin (p70), causing Nijmegen Breakage Syndrome (NBS), is involved in DDR and cell fate upon DNA damage, we used two (S4 and S3R) spontaneously immortalized T cell lines from NBS patients, with the founding mutation and a control cell line (L5).
Nijmegen breakage syndrome 1 (NBS1), a vital DNA repair protein in the homologous recombination repair pathway and a signal modifier in the intra-S phase checkpoint, plays a critical role in cellular response to DNA damages and the maintenance of genomic stability.
Regulation of the Nijmegen breakage syndrome 1 gene NBS1 by c-myc, p53 and coactivators mediates estrogen protection from DNA damage in breast cancer cells.
The results show that p70-nibrin is degraded by the proteasome with varying efficiency in cell lines from different NBS patients leading to lower or higher steady state levels of this partially active protein fragment.
CtIP plays an important role in homologous recombination (HR)-mediated DNA double-stranded break (DSB) repair and interacts with Nbs1 and BRCA1, which are linked to Nijmegen breakage syndrome (NBS) and familial breast cancer, respectively.
Analysis of the functional consequences of the identified NBS1 mutations in Mre11-binding domain showed loss of nuclear localization of Nbs1 partner Mre11, one of the hallmarks for Nbs1 deficiency, in one HCC and two ICCs with NBS1 mutations.
Many studies were published to evaluate the association between Nijmegen breakage syndrome 1 (NBS1) 657del5 polymorphism and breast cancer risk, but the results remained inconsistent.