|
General Comment |
FIGNL1-containing protein complex is required for efficient homologous recombination repair. Yuan J et al. (2013) The RAD51 recombinase plays a central role in homologous recombination (HR), which is critical for repair of DNA double-strand breaks, maintenance of genomic stability, and prevention of developmental disorders and cancer. Here, we report the identification of an RAD51-binding protein fidgetin-like 1 (FIGNL1). FIGNL1 specifically interacts with RAD51 through its conserved RAD51 binding domain. Cells depleted of FIGNL1 show defective HR repair. Interestingly, FIGNL1 is recruited to sites of DNA damage in a manner that is independent of breast cancer 2, early onset, RAD51, and probably, RAD51 paralogs. Conversely, FIGNL1 depletion does not affect the loading of RAD51 onto ssDNA. Our additional analysis uncovered KIAA0146, also known as scaffolding protein involved in DNA repair (SPIDR), as a binding partner of FIGNL1 and established that KIAA0146/SPIDR acts with FIGNL1 in HR repair. Collectively, our study uncovers a protein complex, which consists of FIGNL1 and KIAA0146/SPIDR, in DNA repair and provides potential directions for cancer diagnosis and therapy.//////////////////
|
|
Comment |
Comparative proteomic analysis of primordial follicles from ovaries of immature and aged rats. Govindaraj V et al. (2015) Age related decline in reproductive performance in women is well documented and apoptosis has been considered as one of the reasons for the decline of primordial follicle reserve. Recently we observed a decline in the efficiency of DNA repair ability in aged rat primordial follicles as demonstrated by decreased mRNA levels of DNA repair genes BRCA1 and H2AX. In the present study, a two-dimensional electrophoresis (2DE) proteomic approach was employed to identify differentially expressed proteins in primordial follicles isolated from ovaries of immature (ā¼20 days) and aged (ā¼400-450 days) rats. Using MALDI-TOF/TOF MS, we identified 13 differentially expressed proteins (pā<ā0.05) which included seven up-regulated and six down-regulated proteins in aged primordial follicles. These proteins are involved in a wide range of biological functions including apoptosis, DNA repair, and the immune system. Interestingly, the differentially expressed proteins such as FIGNL1 (DNA repair) and BOK (apoptotic protein) have not been previously reported in the rat primordial follicles and these proteins can be related to some common features of ovarian aging such as loss of follicle reserve and genome integrity. The quantitative differences of two important proteins BOK and FIGNL1 observed by the proteomic analysis were correlated with the transcript levels, as determined by semi-quantitative RT-PCR. Our results improve the current knowledge about protein factors associated with molecular changes in rat primordial follicles as a function of aging and our understanding of the proteomic processes involved in degenerative changes observed in aging primordial follicles.//////////////////
|