ORC proteins in the mammalian zygote

Abstract

Summary The origin recognition complex (ORC) proteins, ORC1-6, are the first proteins that bind DNA replication origins to mark the competency for the initiation of DNA synthesis. These proteins have complex mechanisms of assembly into the ORC complex, and unexpected localizations in the mitotic chromosomes, cytoplasm, and nuclear structures. The mammalian zygote is a potentially important model that may contribute to our understanding of the mechanisms and features influencing origin establishment, and in identifying other functions of the ORC proteins. Along with expected localizations to the chromatin during G1, we found unexpected distribution in the cytoplasm that appeared to accumulate ORC proteins, which suggest potential roles for ORC subunits in mitosis and chromatin segregation. ORC1, 2, 3 and 5 all localize to the area between the separating maternal chromosomes shortly after fertilization. ORC4 forms a cage around the set of chromosomes that will be extruded during polar body formation before it binds to the chromatin shortly before zygotic DNA replication. These data suggest that the ORC proteins may also play roles in preparing the cell for DNA replication in addition to their direct role in establishing functional replication origins.

A lack of coordination between sister-chromatids segregation and cytokinesis in the oocytes of B6.YTIR (XY) sex-reversed female mice

“…F-actin is essential for ARP2 localization and plays a key role in the asymmetric division and polar body extrusion 50 , 51 . ORC4 is a subunit of the origin recognition complex (ORC) but may play a role in the oocyte outside of DNA replication; ORC4 is localized along the oolemma in the GV-oocyte and forms an ovoid structure surrounding the extruding anaphase chromosomes during both meiotic divisions 37 , 52 . In our study, the MII-oocytes from XY females showed similar localization of ORC4, ARP2, and F-actin to those from XX females, suggesting that cortical localization of the MII-spindle and its downstream RanGTP gradient –ARP2/3 pathway was largely normal.…”

Dynamic changes in the transcriptome of oocytes during adolescent-onset PCOS in mice

“…2020), and also affected the balance of epigenetic regulation (S hen and S pruck 2017). ORC proteins can bind DNA replication origins to initiate DNA synthesis, and ORC is especially important in controlling centriole and centrosome copy number (O rtega et al . 2016).…”

Nonreplicative functions of the origin recognition complex

“…Recently, Dr. Ward with colleagues [115] showed that after fertilization, the ORC1, 2, 3, and 5 proteins localize between the separating maternal chromosomes, while the ORC6 subunit is localized to the periphery of the nucleoli at all zygotic stages. This unexpected distribution of ORC proteins suggest their potential roles in mitosis and chromatin segregation in the mammalian zygote [115]. …”