| First Author | Naito Y | Year | 2013 |
| Journal | Cell Cycle | Volume | 12 |
| Issue | 11 | Pages | 1773-84 |
| PubMed ID | 23656780 | Mgi Jnum | J:297173 |
| Mgi Id | MGI:6473851 | Doi | 10.4161/cc.24878 |
| Citation | Naito Y, et al. (2013) Recruitment of cyclin G2 to promyelocytic leukemia nuclear bodies promotes dephosphorylation of gammaH2AX following treatment with ionizing radiation. Cell Cycle 12(11):1773-84 |
| abstractText | Cyclin G2 (CycG2) and Cyclin G1 (CycG1), two members of the Cyclin G subfamily, share high amino acid homology in their Cyclin G boxes. Functionally, they play a common role as association partners of the B''gamma subunit of protein phosphatase 2A (PP2A) and regulate PP2A function, and their expression is increased following DNA damage. However, whether or not CycG1 and CycG2 have distinct roles during the cellular DNA damage response has remained unclear. Here, we report that CycG2, but not CycG1, co-localized with promyelocytic leukemia (PML) and gammaH2AX, forming foci following ionizing radiation (IR), suggesting that CycG2 is recruited to sites of DNA repair and that CycG1 and CycG2 have distinct functions. PML failed to localize to nuclear foci when CycG2 was depleted, and vice versa. This suggests that PML and CycG2 mutually influence each other''s functions following IR. Furthermore, we generated CycG2-knockout (Ccng2 (-/-) ) mice to investigate the functions of CycG2. These mice were born healthy and developed normally. However, CycG2-deficient mouse embryonic fibroblasts displayed an abnormal response to IR. Dephosphorylation of γH2AX and checkpoint kinase 2 following IR was delayed in Ccng2 (-/-) cells, suggesting that DNA damage repair may be perturbed in the absence of CycG2. Although knockdown of B''gamma in wild-type cells also delayed dephosphorylation of gammaH2AX, knockdown of B''gamma in Ccng2 (-/-) cells prolonged this delay, suggesting that CycG2 cooperates with B''gamma to dephosphorylate gammaH2AX. Taken together, we conclude that CycG2 is localized at DNA repair foci following DNA damage, and that CycG2 regulates the dephosphorylation of several factors necessary for DNA repair. |
