Dynamic of centromere associated RNAs and the centromere loading of DNA repair proteins in growing oocytes

Abstract

Mammalian centromeres are generally composed of dispersed repeats and the satellites such as α-satellites in human and major/minor satellites in mouse. Transcription of centromeres by RNA polymerase II is evolutionary conserved and critical for kinetochore assembly. In addition, it has been found that the transcribed satellite RNAs can bind DNA repair proteins such as MRE11 and PRKDC, and excessively expressed satellite RNAs could induce genome instability and facilitate tumorigenesis. During the maturation of female oocyte, centromeres are critical for accurate segregation of homologous chromosomes and sister chromatids. However, the dynamics of oocyte centromere transcription and whether it associated with DNA repair proteins are unknown. In this study, we found the transcription of centromeres is active in growing oocytes but it is silenced when oocytes are fully grown. DNA repair proteins like Mlh1, Mre11 and Prkdc are found associated with the minor satellites and this association can be interfered by RNA polymerase II inhibitor α-amanitin. When the growing oocyte is in vitro matured, Mlh1/Mre11/Prkdc foci would release from centromeres to the ooplasm. If the oocytes are treated with Mre11 inhibitor Mirin, the meiosis resumption of growing oocytes with Mre11 foci can be suppressed. These data revealed the dynamic of centromeric transcription in oocytes and its potential association with DNA repair proteins, which provide clues about how oocytes maintain centromere stability and assemble kinetochores.

Comprehensive modular analyses of scar subtypes illuminate underlying molecular mechanisms and potential therapeutic targets

“…These are potentially associated with inflammatory skin conditions such as eczema and psoriasis. DNA repair and genome stability: Genes such as BRCA1, DHX15, PRKDC and CBL participate in DNA repair and the maintenance of genome stability. These genes could have significant roles in the development of skin cancer and other genetic skin disorders 64–66 …”

“…These genes could have significant roles in the development of skin cancer and other genetic skin disorders. [64][65][66] The Over Representation Analysis indicates that the package identified module M8 (Figure 5E). The top 11 genes were linked with several mechanisms, immune and inflammatory response, epigenetic regulation, cell signalling and cellular processes and transport mechanisms.…”