Cell cycle regulation in response to DNA damage in mammalian cells: A historical perspective

1995 ◽  
Vol 14 (1) ◽  
pp. 17-29 ◽  
Author(s):  
John P. Murnane
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Mammalian Cells ◽  
Cell Cycle Regulation ◽  
Historical Perspective ◽  
Cycle Regulation

Calcium and cell cycle control

Development ◽  
1990 ◽  
Vol 108 (4) ◽  
pp. 525-542 ◽  
Author(s):  
M. Whitaker ◽  
R. Patel
Keyword(s):  
Cell Cycle ◽  
Sea Urchin ◽  
Mammalian Cells ◽  
Cell Cycle Regulation ◽  
Sea Urchins ◽  
Cell Cycle Control ◽  
Control Point ◽  
Control Cell ◽  
Free Calcium ◽  
Cycle Regulation

The cell division cycle of the early sea urchin embryo is basic. Nonetheless, it has control points in common with the yeast and mammalian cell cycles, at START, mitosis ENTRY and mitosis EXIT. Progression through each control point in sea urchins is triggered by transient increases in intracellular free calcium. The Cai transients control cell cycle progression by translational and post-translational regulation of the cell cycle control proteins pp34 and cyclin. The START Cai transient leads to phosphorylation of pp34 and cyclin synthesis. The mitosis ENTRY Cai transient triggers cyclin phosphorylation. The motosis EXIT transient causes destruction of phosphorylated cyclin. We compare cell cycle regulation by calcium in sea urchin embryos to cell cycle regulation in other eggs and oocytes and in mammalian cells.

scholarly journals Babam2 Regulates Cell Cycle Progression and Pluripotency in Mouse Embryonic Stem Cells as Revealed by Induced DNA Damage

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 397
Author(s):  
Cheuk Yiu Tenny Chung ◽  
Paulisally Hau Yi Lo ◽  
Kenneth Ka Ho Lee
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Dna Damage ◽  
Gamma Irradiation ◽  
Cellular Senescence ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Embryonic Stem ◽  
Cycle Progression ◽  
Cycle Regulation

BRISC and BRCA1-A complex member 2 (Babam2) plays an essential role in promoting cell cycle progression and preventing cellular senescence. Babam2-deficient fibroblasts show proliferation defect and premature senescence compared with their wild-type (WT) counterpart. Pluripotent mouse embryonic stem cells (mESCs) are known to have unlimited cell proliferation and self-renewal capability without entering cellular senescence. Therefore, studying the role of Babam2 in ESCs would enable us to understand the mechanism of Babam2 in cellular aging, cell cycle regulation, and pluripotency in ESCs. For this study, we generated Babam2 knockout (Babam2−/−) mESCs to investigate the function of Babam2 in mESCs. We demonstrated that the loss of Babam2 in mESCs leads to abnormal G1 phase retention in response to DNA damage induced by gamma irradiation or doxorubicin treatments. Key cell cycle regulators, CDC25A and CDK2, were found to be degraded in Babam2−/− mESCs following gamma irradiation. In addition, Babam2−/− mESCs expressed p53 strongly and significantly longer than in control mESCs, where p53 inhibited Nanog expression and G1/S cell cycle progression. The combined effects significantly reduced developmental pluripotency in Babam2−/− mESCs. In summary, Babam2 maintains cell cycle regulation and pluripotency in mESCs in response to induced DNA damage.

scholarly journals Cilia and the cell cycle?

2005 ◽  
Vol 169 (5) ◽  
pp. 707-710 ◽  
Author(s):  
Lynne M. Quarmby ◽  
Jeremy D.K. Parker
Keyword(s):  
Cell Cycle ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Mammalian Cells ◽  
Cell Cycle Regulation ◽  
Polycystic Kidney ◽  
Unicellular Alga ◽  
Regulatory Relationship ◽  
Cycle Regulation ◽  
Multiple Signaling

A recent convergence of data indicating a relationship between cilia and proliferative diseases, such as polycystic kidney disease, has revived the long-standing enigma of the reciprocal regulatory relationship between cilia and the cell cycle. Multiple signaling pathways are localized to cilia in mammalian cells, and some proteins have been shown to act both in the cilium and in cell cycle regulation. Work from the unicellular alga Chlamydomonas is providing novel insights as to how cilia and the cell cycle are coordinately regulated.

scholarly journals PCNA-Mediated Degradation of p21 Coordinates the DNA Damage Response and Cell Cycle Regulation in Individual Cells

Cell Reports ◽  
2019 ◽  
Vol 27 (1) ◽  
pp. 48-58.e7 ◽  
Author(s):  
Caibin Sheng ◽  
Isabella-Hilda Mendler ◽  
Sara Rieke ◽  
Petra Snyder ◽  
Marcel Jentsch ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Cell Cycle Regulation ◽  
Damage Response ◽  
Cycle Regulation

Dose Escalated RAD001 (Everolimus) Enhances Chemosensitivity in Precursor-B Acute Lymphoblastic Leukemia, through a JNK Dependent Suppression of Cell Cycle Checkpoint Regulation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1604-1604
Author(s):  
Philip O. Saunders ◽  
Kenneth F. Bradstock ◽  
Linda J. Bendall
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Regulation ◽  
Cell Cycle Checkpoint ◽  
G2 Arrest ◽  
Jnk Pathway ◽  
Microtubule Disruption ◽  
Cell Kill ◽  
Cycle Checkpoint ◽  
Cycle Regulation

Abstract Five year survival for patients with relapsed pre-B ALL remains less than 10%, requiring new approaches to therapy. We sought to evaluate the potential of mTOR inhibitor RAD001 to enhance pre-B ALL cell killing by agents that induce DNA damage or microtubule disruption and identify interactions that may indicate novel approaches to therapy. Combining 16μM RAD001 with agents that cause DNA damage or microtubule disruption in vitro, enhanced caspase-dependent killing (p<0.05) of pre-B ALL cells. We observed 16μM RAD001 suppressed p53 and markedly attenuated p21 responses to DNA damage or vincristine. Lentiviral siRNA knock down of p53 in Nalm6 cells led to significantly increased (p<0.05) cell kill by vincristine relative to luciferase knockdown cells with an intact p53 response. This data indicates enhanced killing by combining RAD001 with DNA damage or vincristine does not require p53. Intracellular flow cytometry revealed that combining 16μM RAD001 with DNA damage or vincristine activates the JNK pathway. c-Jun has been reported to promote proliferation, apoptosis, suppress p53 and p21 promoters and prolong the half-life of p53 analogue, p73. Concordantly, we observed up regulation of p73, puma, bax, bim and cleaved caspase 3, associated with enhanced cell death. This data indicates that p73 provides an alternate pathway to apoptosis. We hypothesized that 16μM RAD001 enhances chemosensitivity through a JNK dependent suppression of cell cycle checkpoint regulation. We observed 1.5μM RAD001 inhibited pRb, Ki67 and PCNA expression, increasing G0/1 cell cycle arrest in response to DNA damage or vincristine, however 16μM RAD001 increased pRb, cyclin D1, Ki67, active CDC2 and PCNA expression. Increased DNA content, BrdU uptake and PCNA expression indicate cell cycle progression occurs in the presence of DNA damage or vincristine, when combined with 16μM RAD001. To validate the role of the JNK pathway in enhancing chemosensitivity we evaluated the impact of JNK inhibition on cell cycle regulation and cell survival. We observed enhanced cell cycle checkpoint regulation, indicated by reduced expression of c-jun, pRb, PCNA and Ki67 in Nalm6 cells. Furthermore, JNK inhibition enhanced G0/1 or G2 arrest in response to DNA damage in Nalm6 and REH cell lines respectively and enhanced G2 arrest in response to vincristine. JNK inhibition led to reduced cell kill by DNA damage or microtubule disruption in Nalm6 and REH cell lines. This data strongly suggests that impaired cell cycle regulation by 16μM RAD001 is mediated through a JNK dependent mechanism. We conclude that dose escalated RAD001 enhances chemosensitivity independently of p53, through a JNK dependent impairment of cell cycle regulation, in response to DNA damage or microtubule disruption. Our data indicates that dose escalated RAD001 has the potential to enhance chemosensitivity in patients with pre-B ALL and provides a rationale for combining agents which induce JNK activation with DNA damage or microtubule disruption, as a therapeutic strategy in pre-B ALL.

SP-02: Cell Cycle Regulation of the DNA Damage Response: Targeting WEE1 Kinase to Impair DNA Repair.

2012 ◽  
Vol 104 ◽  
pp. 21
Author(s):  
M.A.T.M. Van Vugt ◽  
M. Krajewska ◽  
H. Sillje ◽  
A.M. Heijink ◽  
Y. Bisselink ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Repair ◽  
Dna Damage Response ◽  
Cell Cycle Regulation ◽  
Damage Response ◽  
Wee1 Kinase ◽  
Cycle Regulation
Sign in / Sign up

Export Citation Format

Share Document