Rabbit Anti-Human LIG4 (a.a. 1-609) Polyclonal antibody

The non-homologous end-joining (NHEJ) pathway of DNA recombination is important for genomic stability in animal cells, since the absence of Ku70, Ku80, Lig4 or Xrcc4 results in non-reciprocal translocation and chromosome fragmentation. The role of LIG4 in the genomic instability of Candida albicans has been analyzed. We have found that both cell transformation and 5'-fluoroorotic acid selection steps used to obtain several lig4 mutants (LIG4/lig4 Ura(+); LIG4/lig4 Ura(-); lig4/lig4 Ura(+); lig4/lig4 Ura(-); and revertant lig4/LIG4 Ura(+)) resulted in significant alterations in chromosome R (ChrR). However, this effect is not specific for LIG4, since disruption of SHE9, a gene unrelated to recombination, also caused alterations in the mobility of ChrR. On the other hand, we could not detect reciprocal or non-reciprocal translocations between non-homologous chromosomes in several lig4 mutants. Furthermore, propagation of these mutants in rich medium did not cause other alterations in the mobility of ChrR. Adaptive mutagenesis of C albicans, determined by the appearance Of L-sorbose-utilizing mutants on L-sorbose plates, was also independent of the presence of Lig4 and occurred by monosomy of Chr5. Accordingly, the NHEJ pathway does not appear to be involved in the adaptive mutagenesis mediated by alterations in chromosome copy number. (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.

In Philadelphia chromosome-negative myeloproliferative neoplasms (Ph- MPN), non-specific chromosomal defects are detectable and essential thrombocythemia (ET) has the lowest rate of aberrations, whereas primary myelofibrosis (PMF) and post-polycythemia vera (PV) myelofibrosis have the highest rates of aberrations. The frequency of cytogenetic defects in pre-fibrotic stage PMF has not been characterized thus far and the underlying molecular defects of chromosomal instability are unknown. In this study, histopathological findings were correlated with cytogenetic data (n = 249). The expression of DNA repair factors ERCC1 and LIG4 were determined in Ph- MPN with and without cytogenetic aberrations. Pre-fibrotic PMF and ET have similarly low frequencies of karyotype anomalies. The expression of ERCC1, but not LIG4, is increased in fibrotic stage PMF but is not associated with accumulation of cytogenetic defects. In conclusion, aberrant karyotypes in Ph- MPN reflect the chromosomal instability in these diseases and, in comparison with pre-fibrotic stages, Ph- MPN with fibrosis has the highest frequency of cytogenetic aberrations.