Tissue-Specific Requirement for the GINS Complex During Zebrafish Development

Abstract

Efficient and accurate DNA replication is particularly critical in stem and progenitor cells for successful proliferation and survival. The replisome, an amalgam of protein complexes, is responsible for binding potential origins of replication, unwinding the double helix, and then synthesizing complimentary strands of DNA. According to current models, the initial steps of DNA unwinding and opening are facilitated by the CMG complex, which is composed of a GINS heterotetramer that connects Cdc45 with the mini-chromosome maintenance (Mcm) helicase. In this work, we provide evidence that in the absence of GINS function DNA replication is cell autonomously impaired, and we also show that gins1 and gins2 mutants exhibit elevated levels of apoptosis restricted to actively proliferating regions of the central nervous system (CNS). Intriguingly, our results also suggest that the rapid cell cycles during early embryonic development in zebrafish may not require the function of the canonical GINS complex as neither zygotic Gins1 nor Gins2 isoforms seem to be present during these stages.

The replicative helicase CMG is required for the divergence of cell fates during asymmetric cell divisionin vivo

“…Together, these findings suggest that in the context of asymmetric cell division, CMG has a conserved role in the divergence of cell fates that is distinct from its conserved role in DNA unwinding. Finally, the idea that CMG has a conserved role in cell fate is supported by previous observations implicating Psf2 GINS2 in nervous system development in Xenopus and zebrafish 51,52 , Sld5 GINS4 in early embryonic development and nervous system development in mouse 53,54 and MCM5 in neuronal differentiation in Drosophila 55 .…”

PAX5 and circ1857 affected DLBCL progression and B‐cell proliferation through regulating GINS1

“…From an oncological view, aberrant high expression of PAX5 and GINS1 blocked B-cell differentiation. In addition, GINS1 recently was reported to have anti-apoptotic functions, 48,49 all these findings sug-…”

“…From an oncological view, aberrant high expression of PAX5 and GINS1 blocked B‐cell differentiation. In addition, GINS1 recently was reported to have anti‐apoptotic functions, 48,49 all these findings suggested that deregulated PAX5 and GINS1 are an oncogene for a fraction of DLBCL. Furthermore more cell lines, more tissue samples and further studies are needed to establish the therapeutic potential of GINS1 in DLBCL.…”

Complementary biomarkers of computed tomography for diagnostic grading of gastric cancer: DSCC1 and GINS1

“…This is critical in ensuring that newly formed cells have accurate genetic information after each cell division [ 27 ]. GINS1’s expression is related to different stages of the cell cycle, especially during the S phase (DNA replication) and M phase (mitosis), where it plays an essential role in aiding DNA replication and ensuring proper chromosome separation [ 28 ]. Dysfunctional GINS1 may lead to DNA replication errors, chromosome instability, and cell cycle issues, highly relevant to various diseases, including cancer.…”