Biomedical subjects

Mila Jankovic

Publications and source records attributed to Mila Jankovic.

3 recordsLinked to original sources

PubMed2003

Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand.

Somatic hypermutation and class switch recombination are DNA modification reactions that alter the genes encoding antibodies in B lymphocytes. Both of these distinct reactions require activation-induced deaminase (AID) and transcription. Here we show that in Escherichia coli, as in eukaryotic cells, the mutation frequency is directly proportional to the transcription of target genes. Transcription enhances mutation of the nontemplate DNA strand, which is exposed as single-stranded DNA during the elongation reaction, but not mutation of the template DNA strand, which is protected by E. coli RNA polymerase. Our results establish a direct link between AID and transcription and suggest that the role of transcription in facilitating mutation is to provide AID with access to single-stranded DNA.

Animals↗

PubMed2003

OcaB regulates transitional B cell selection.

OcaB, also known as Bob-1 or Obf-1, is a transcriptional co-activator which regulates Igkappa gene transcription, recombination and receptor editing; it is required for normal development of transitional B cells and for germinal center formation. Here we report that abnormal B cell development in OcaB(-/-) mice results in a skewed Igkappa repertoire including anti-DNA antibodies, suggesting that OcaB is essential for antibody repertoire selection. To determine whether OcaB is required for BCR-mediated B cell selection, we introduced a pre-recombined alpha hen egg lysozyme (HEL) Ig transgene into OcaB(-/-) mice. We find that in OcaB(-/-) mice expressing transgenic alphaHEL Ig bone marrow B cell development is normal up to the immature B cell stage, but fails to progress to the transitional B cell stage. We conclude that OcaB is required for normal selection of the antibody repertoire in developing B cells.

Animals↗

PubMed2002

OcaB is required for normal transcription and V(D)J recombination of a subset of immunoglobulin kappa genes.

OcaB, a transcriptional coactivator also known as Bob-1 or OBF-1, was isolated on the basis of its ability to enhance transcription of immunoglobulin (Ig) genes in vitro. Paradoxically, OcaB(-/-) mice showed no apparent deficiency in Ig gene transcription, only cellular immune defects including absence of germinal centers (GC) and decreased numbers of immature B cells; the genes targeted by OcaB were not determined. Here we report that OcaB is essential for V(D)J recombination of a subset of Igkappa genes. We show that OcaB modulates recombination by directly enhancing Igkappa gene transcription in vivo.

Animals↗