Che-1/AATF, a multivalent adaptor connecting transcriptional regulation, checkpoint control, and apoptosisThis paper is one of a selection of papers published in this Special Issue, entitled 28th International West Coast Chromatin and Chromosome Conference, and has undergone the Journal's usual peer review process.

2007 ◽  
Vol 85 (4) ◽  
pp. 477-483 ◽  
Author(s):  
Claudio Passananti ◽  
Aristide Floridi ◽  
Maurizio Fanciulli
Keyword(s):  
Cell Cycle ◽  
Transcriptional Regulation ◽  
Rna Polymerase Ii ◽  
Cell Cycle Progression ◽  
Peer Review Process ◽  
Cell Cycle Checkpoint ◽  
Checkpoint Control ◽  
Interacting Protein ◽  
Cycle Checkpoint ◽  
Viral Factor

Che-1/AATF (Che-1) was originally characterized as an interacting protein for RNA polymerase II. In addition to transcriptional regulation, the evidence suggests that Che-1 has a viral factor-like S phase promoting role in counteracting Rb repression to facilitate E2F-dependent transactivation during G1–S transition. Recently, Che-1 was found to play an important role in the DNA damage response and cell-cycle checkpoint control. Genetic studies in mice revealed that Che-1 is essential for preimplantation development and the establishment of embryonic gene expression. Importantly, several findings showed that Che-1 participates in inhibiting apoptotic process. Thus, Che-1 emerges as an important adaptor that connects transcriptional regulation, cell-cycle progression, checkpoint control, and apoptosis.

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.

scholarly journals DNA Damage-Induced Cell Cycle Checkpoint Control Requires CtIP, a Phosphorylation-Dependent Binding Partner of BRCA1 C-Terminal Domains

2004 ◽  
Vol 24 (21) ◽  
pp. 9478-9486 ◽  
Author(s):  
Xiaochun Yu ◽  
Junjie Chen
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Molecular Mechanisms ◽  
Cell Cycle Checkpoint ◽  
Dependent Manner ◽  
Checkpoint Control ◽  
Interacting Protein ◽  
Binding Partner ◽  
Cycle Checkpoint ◽  
Multiple Cell

ABSTRACT The BRCA1 C-terminal (BRCT) domain has recently been implicated as a phospho-protein binding domain. We demonstrate here that a CTBP-interacting protein CtIP interacts with BRCA1 BRCT domains in a phosphorylation-dependent manner. The CtIP/BRCA1 complex only exists in G2 phase and is required for DNA damage-induced Chk1 phosphorylation and the G2/M transition checkpoint. However, the CtIP/BRCA1 complex is not required for the damage-induced G2 accumulation checkpoint, which is controlled by a separate BRCA1/BACH1 complex. Taken together, these data not only implicate CtIP as a critical player in cell cycle checkpoint control but also provide molecular mechanisms by which BRCA1 controls multiple cell cycle transitions after DNA damage.

scholarly journals Acceleration or Brakes: Which Is Rational for Cell Cycle-Targeting Neuroblastoma Therapy?

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 750
Author(s):  
Kiyohiro Ando ◽  
Akira Nakagawara
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Progression ◽  
Parp Inhibitors ◽  
Cell Cycle Checkpoint ◽  
Mitotic Catastrophe ◽  
Malignant Neoplasms ◽  
Checkpoint Kinases ◽  
Molecular Features ◽  
Cycle Checkpoint

Unrestrained proliferation is a common feature of malignant neoplasms. Targeting the cell cycle is a therapeutic strategy to prevent unlimited cell division. Recently developed rationales for these selective inhibitors can be subdivided into two categories with antithetical functionality. One applies a “brake” to the cell cycle to halt cell proliferation, such as with inhibitors of cell cycle kinases. The other “accelerates” the cell cycle to initiate replication/mitotic catastrophe, such as with inhibitors of cell cycle checkpoint kinases. The fate of cell cycle progression or arrest is tightly regulated by the presence of tolerable or excessive DNA damage, respectively. This suggests that there is compatibility between inhibitors of DNA repair kinases, such as PARP inhibitors, and inhibitors of cell cycle checkpoint kinases. In the present review, we explore alterations to the cell cycle that are concomitant with altered DNA damage repair machinery in unfavorable neuroblastomas, with respect to their unique genomic and molecular features. We highlight the vulnerabilities of these alterations that are attributable to the features of each. Based on the assessment, we offer possible therapeutic approaches for personalized medicine, which are seemingly antithetical, but both are promising strategies for targeting the altered cell cycle in unfavorable neuroblastomas.

scholarly journals A DNA-Damage-Induced Cell Cycle Checkpoint in Arabidopsis

Genetics ◽  
2003 ◽  
Vol 164 (1) ◽  
pp. 323-334
Author(s):  
S B Preuss ◽  
A B Britt
Keyword(s):  
Cell Cycle ◽  
Gamma Radiation ◽  
Cell Cycle Progression ◽  
Cell Cycle Checkpoint ◽  
Phase Cell ◽  
Cycle Arrest ◽  
Cycle Checkpoint ◽  
Radiation Induced ◽  
High Doses ◽  
Regulation Of Cell Cycle

Abstract Although it is well established that plant seeds treated with high doses of gamma radiation arrest development as seedlings, the cause of this arrest is unknown. The uvh1 mutant of Arabidopsis is defective in a homolog of the human repair endonuclease XPF, and uvh1 mutants are sensitive to both the toxic effects of UV and the cytostatic effects of gamma radiation. Here we find that gamma irradiation of uvh1 plants specifically triggers a G2-phase cell cycle arrest. Mutants, termed suppressor of gamma (sog), that suppress this radiation-induced arrest and proceed through the cell cycle unimpeded were recovered in the uvh1 background; the resulting irradiated plants are genetically unstable. The sog mutations fall into two complementation groups. They are second-site suppressors of the uvh1 mutant's sensitivity to gamma radiation but do not affect the susceptibility of the plant to UV radiation. In addition to rendering the plants resistant to the growth inhibitory effects of gamma radiation, the sog1 mutation affects the proper development of the pollen tetrad, suggesting that SOG1 might also play a role in the regulation of cell cycle progression during meiosis.

Search, capture and signal: games microtubules and centrosomes play

2001 ◽  
Vol 114 (2) ◽  
pp. 247-255 ◽  
Author(s):  
S.C. Schuyler ◽  
D. Pellman
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cytoplasmic Dynein ◽  
Cell Cycle Checkpoint ◽  
Cellular Polarity ◽  
Cycle Progression ◽  
Cycle Checkpoint ◽  
Dividing Cells ◽  
Actin Cables ◽  
Type V

Accurate distribution of the chromosomes in dividing cells requires coupling of cellular polarity cues with both the orientation of the mitotic spindle and cell cycle progression. Work in budding yeast has demonstrated that cytoplasmic dynein and the kinesin Kip3p define redundant pathways that ensure proper spindle orientation. Furthermore, it has been shown that the Kip3p pathway components Kar9p and Bim1p (Yeb1p) form a complex that provides a molecular link between cortical polarity cues and spindle microtubules. Recently, other studies indicated that the cortical localization of Kar9p depends upon actin cables and Myo2p, a type V myosin. In addition, a BUB2-dependent cell cycle checkpoint has been described that inhibits the mitotic exit network and cytokinesis until proper centrosome position is achieved. Combined, these studies provide molecular insight into how cells link cellular polarity, spindle position and cell cycle progression.

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.

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