22 research outputs found
The XPF-ERCC1 endonuclease and homologous recombination contribute to the repair of minor groove DNA interstrand crosslinks inmammalian cells produced by the pyrrolo[2,1-c][1,4]benzodiazepine dimer SJG-136
SJG-136, a pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer, is a highly efficient interstrand crosslinking agent that reacts with guanine bases in a 5'-GATC-3' sequence in the DNA minor groove. SJG-136 crosslinks form rapidly and persist compared to those produced by conventional crosslinking agents such as nitrogen mustard, melphalan or cisplatin which bind in the DNA major groove. A panel of Chinese hamster ovary (CHO) cells with defined defects in specific DNA repair pathways were exposed to the bi-functional agents SJG-136 and melphalan, and to their mono-functional analogues mmy-SJG and mono-functional melphalan. SJG-136 was >100 times more cytotoxic than melphalan, and the bi-functional agents were much more cytotoxic than their respective mono-functional analogues. Cellular sensitivity of both SJG-136 and melphalan was dependent on the XPF-ERCC1 heterodimer, and homologous recombination repair factors XRCC2 and XRCC3. The relative level of sensitivity of these repair mutant cell lines to SJG-136 was, however, significantly less than with major groove crosslinking agents. In contrast to melphalan, there was no clear correlation between sensitivity to SJG-136 and crosslink unhooking capacity measured using a modified comet assay. Furthermore, repair of SJG-136 crosslinks did not involve the formation of DNA double-strand breaks. SJG-136 cytotoxicity is likely to result from the poor recognition of DNA damage by repair proteins resulting in the slow repair of both mono-adducts and more importantly crosslinks in the minor groove
Mutations in the promoter region of the androgen receptor gene are not common in males with idiopathic infertility
Mutations in the promoter region of the androgen receptor gene are not common in males with idiopathic infertility
Molecular Human Reproduction53287-290MHRE
Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion
Molecular Human Reproduction48763-768MHRE
A genomic region encoding stonefish (Synanceja horrida) stonustoxin beta-subunit contains an intron
10.1016/0041-0101(94)90329-8Toxicon32121684-1688TOXI
Male infertility and the androgen receptor: Molecular, clinical and therapeutic aspects
Reproductive Medicine Review62113-131RMER
Towards understanding of laccase-catalysed oxidative oligomerisation of dimeric lignin model compounds
10.1039/c6ra26975cRSC Advances72011951-1195
Partial androgen insensitivity and correlations with the predicted three dimensional structure of the androgen receptor ligand-binding domain
10.1016/S0303-7207(97)00229-3Molecular and Cellular Endocrinology137141-50MCEN
Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility
Journal of Clinical Endocrinology and Metabolism82113777-3782JCEM
Human androgen receptor mutation disrupts ternary interactions between ligand, receptor domains, and the coactivator TIF2 (transcription intermediary factor 2)
10.1210/me.14.8.1187Molecular Endocrinology1481187-1197MOEN