Sequential loss of cell cycle checkpoint control contributes to malignant transformation of murine embryonic fibroblasts induced by 20-methylcholanthrene

2010 ◽  
pp. n/a-n/a ◽  
Author(s):  
Sudeshna Mukherjee ◽  
Sugata Manna ◽  
Debolina Pal ◽  
Pratima Mukherjee ◽  
Chinmay K. Panda
Keyword(s):  
Cell Cycle ◽  
Malignant Transformation ◽  
Cell Cycle Checkpoint ◽  
Checkpoint Control ◽  
Embryonic Fibroblasts ◽  
Sequential Loss ◽  
Cycle Checkpoint

DNA damage checkpoint kinases in cancer

2020 ◽  
Vol 22 ◽  
Author(s):  
Hannah L. Smith ◽  
Harriet Southgate ◽  
Deborah A. Tweddle ◽  
Nicola J. Curtin
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Environmental Dna ◽  
Cell Cycle Checkpoint ◽  
Checkpoint Control ◽  
Integrated Network ◽  
Checkpoint Kinases ◽  
G1 Checkpoint ◽  
Cycle Checkpoint ◽  
High Level

Abstract DNA damage response (DDR) pathway prevents high level endogenous and environmental DNA damage being replicated and passed on to the next generation of cells via an orchestrated and integrated network of cell cycle checkpoint signalling and DNA repair pathways. Depending on the type of damage, and where in the cell cycle it occurs different pathways are involved, with the ATM-CHK2-p53 pathway controlling the G1 checkpoint or ATR-CHK1-Wee1 pathway controlling the S and G2/M checkpoints. Loss of G1 checkpoint control is common in cancer through TP53, ATM mutations, Rb loss or cyclin E overexpression, providing a stronger rationale for targeting the S/G2 checkpoints. This review will focus on the ATM-CHK2-p53-p21 pathway and the ATR-CHK1-WEE1 pathway and ongoing efforts to target these pathways for patient benefit.

Role played by BRCA1 in transcriptional regulation in response to therapy

2007 ◽  
Vol 35 (5) ◽  
pp. 1342-1346 ◽  
Author(s):  
M.M. Murray ◽  
P.B. Mullan ◽  
D.P. Harkin
Keyword(s):  
Cell Cycle ◽  
Transcriptional Regulation ◽  
Cancer Susceptibility ◽  
Susceptibility Gene ◽  
Breast Cancer Susceptibility ◽  
Cell Cycle Checkpoint ◽  
Response To Therapy ◽  
Breast Cancer Susceptibility Gene ◽  
Checkpoint Control ◽  
Cycle Checkpoint

BRCA1 (breast-cancer susceptibility gene 1) is a tumour suppressor, implicated in the hereditary predisposition to breast and ovarian cancer. BRCA1 has been implicated in a number of cellular processes including DNA repair and recombination, cell cycle checkpoint control, chromatin remodelling and ubiquitination. In addition, substantial data now exist to suggest a role for BRCA1 in transcriptional regulation; BRCA1 has been shown to interact with the Pol II holoenzyme complex and to interact with multiple transcription factors, such as p53 and c-Myc. We have previously identified a range of BRCA1 transcriptional targets and have linked these to specific cellular pathways, including cell cycle checkpoint activation and apoptosis. Current research is focused on the transcriptional mechanisms that underpin the association of BRCA1 deficiency with increased sensitivity to DNA damage-based chemotherapy and resistance to spindle poisons.

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