Elevated Cyclin G2 Expression Intersects with DNA Damage Checkpoint Signaling and Is Required for a Potent G2/M Checkpoint Arrest Response to Doxorubicin

Abstract

Background: DNA damage triggers cell cycle checkpoints to halt cell division ahead of DNA repair. Results: Ectopic cyclin G2 (CycG2) induces a Chk2-dependent cell cycle arrest, and depletion of endogenous CycG2 attenuates doxorubicin-induced G 2 /M-phase cell cycle arrest. Conclusion: CycG2 influences checkpoint signaling and is required for G 2 /M arrest responses to genotoxic stress. Significance: Proper checkpoint function is important for genomic integrity and tumor suppression.

B- myb is an essential regulator of hematopoietic stem cell and myeloid progenitor cell development

“…HSC differentiation is also accompanied by increases in CCNG2, whereas self-renewing HSCs do not exhibit such changes in gene expression (18). CCNG2 is considered an atypical cyclin in that its up-regulation is associated with cell cycle inhibition, and studies have demonstrated the involvement of this gene in the induction and/or maintenance of cell cycle arrest (51). CCNG2 mRNA levels in B-myb-deficient LSK + cells were decreased, and it is therefore possible that B-myb KO HSCs do enter the differentiation program but ultimately fail to complete it.…”

Recruitment of cyclin G2 to promyelocytic leukemia nuclear bodies promotes dephosphorylation of γH2AX following treatment with ionizing radiation

“…36,37 CycG1 and CycG2 contribute to G 2 /M arrest during DDR, but they appear to perform different roles. 27,28 However, little is known about the roles of CycG2, as a CycG2-knockout mouse has not been studied.…”

Time-course Comparison of Gene Expression Profiles Induced by the Genotoxic Hepatocarcinogen, Chrysene, in the Mouse Liver

“…In conclusion, in the present study, we examined by qPCR the time-dependent changes in the gene expression proˆles in the mouse liver during a very early period (4,16,20,24 and 48 h) after chrysene administration. We selected 50 candidate genes which discriminated genotoxic hepatocarcinogens from non-genotoxic hepatocarcinogens based on our previous DNA microarray studies, and we used these to determine the optimal examination time within a short period after the administration of the genotoxic hepatocarcinogen.…”

“…The control animals received olive oil. At 4,16,20,24 and 48 h after treatment, the animals were sacriˆced, and the liver was collected, frozen on dry ice, and stored at -809 C until use.…”

“…qPCR with 33 candidate genes and statistical analysis via PCA successfully diŠerentiate the genotoxic hepatocarcinogens (DEN and 2,6-dinitrotoluene) from the non-genotoxic hepatocarcinogen (DEHP) and the non-genotoxic non-hepatocarcinogen (phenacetin) (10). The present study was a preceding study to determine the optimal examination time within 48 h of the administration of the genotoxic hepatocarcinogen chrysene for the clariˆcation of biomarker genes; to this end, we examined the gene expression proˆles at 4,16,20,24, and 48 h after the administration of this chemical. We supposed that 4 h was the time for DNA damage and repair, 16 h the time for DNA repair for some chemicals (11), 20 h the beginning of cell proliferation, and 24 and 48 h the time of cell proliferation (12,13).…”