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Human CHEK1 Protein expressed in Baculovirus infected Insect Cells - ABIN457519
Larsen, Rampalli, Burns, Brunette, Dilworth, Megeney: Caspase 3/caspase-activated DNase promote cell differentiation by inducing DNA strand breaks. in Proceedings of the National Academy of Sciences of the United States of America 2010
BRCA1 downregulation combined with CHK1 inhibition induced excessive amounts of DNA damage, resulting in an inability to complete the S-phase. Therefore, we suggest CHK1 inhibition as a strategy for targeting BRCA1- or CDK12 (show CRKRS Proteins)-deficient tumors.
PLAUR (show PLAUR Proteins) to be essential for activation of Checkpoint kinase 1 (CHK1); maintenance of cell cycle arrest after DNA damage in a TP53 (show TP53 Proteins)-dependent manner; expression, nuclear import and recruitment to DNA-damage foci of RAD51 (show RAD51 Proteins) recombinase (show RAG1 Proteins), the principal protein involved in the homologous recombination repair pathway.
Results unveil a new aspect of PERK (show EIF2AK3 Proteins) function and previously unknown roles for Claspin and Chk1 as negative regulators of DNA replication in the absence of genotoxic stress.
The findings reveal ATXN3 (show ATXN3 Proteins) to be a novel deubiquitinase of Chk1, providing a new mechanism of Chk1 stabilization in genome integrity maintenance.
Small molecule ATR (show ANTXR1 Proteins) and Chk1 inhibitors potently sensitize lymphoma cells to UVA radiation and induce a prominent apoptotic response
These findings demonstrate an unsuspected requirement for a balanced nucleotide pool for optimal Chk1 activation both in unchallenged cells and in response to genotoxic stress.
ATR (show ANTXR1 Proteins) inhibition potentiated Chk1 inhibitor induced replication stress and cytotoxicity via the abrogation of ATR (show ANTXR1 Proteins)-dependent feedback activation of Chk1 induced by Chk1 inhibitor generated replication stress in tumor cell lines.
CHK1 overexpression is associated with T-cell and Hodgkin Lymphoma.
Date show that when Wee1 (show WEE1 Proteins) alone is inhibited, Chk1 suppresses CDC45 (show CDC45 Proteins) loading and thereby limits the extent of unscheduled replication initiation and subsequent S-phase DNA damage, despite very high CDK (show CDK4 Proteins)-activity.
HPV31 regulates RRM2 (show RRM2 Proteins) levels through expression of E7 and activation of the ATR (show ANTXR1 Proteins)-Chk1-E2F1 (show E2F1 Proteins) DNA damage response, which is essential to combat replication stress upon entry into S-phase.
Inhibition of Drf1 (show DBF4B Proteins) is the primary mechanism by which Chk1 blocks cell-cycle progression in the early embryo and is an essential function of Chk1 at the blastula-to-gastrula stage of development.
The study analyzes the role of Chk1 in the replication program in sperm nuclei replicating in Xenopus egg extracts by a combination of experimental and modelling approaches.
ATR-Chk1 DDR pathway appears to be dispensable for the preferential association of REV1 to MMC-damaged chromatin.
Results show that Chk1 negatively regulates the Treslin-mediated loading of Cdc45 (show CDC45 Proteins) onto chromatin and thereby serves to antagonize the initiation of replication.
The MRN complex, in particular the nuclease (show DCLRE1C Proteins) activity of Mre11 (show MRE11A Proteins), plays an important role in the activation of Chk1 in response to stalled replication forks.
DNA polymerase kappa (show POLK Proteins)-dependent DNA synthesis at stalled replication forks is important for CHK1 activation.
APE2 (show APEX2 Proteins) associates with Chk1; a serine residue (S86) in the Chk1-binding motif of APE2 (show APEX2 Proteins) is essential for Chk1 phosphorylation, indicating a Claspin-like but distinct role for APE2 (show APEX2 Proteins) in ATR-Chk1 signaling.
Data show that the death pathway is independent of ERK (show MAPK1 Proteins) but relies on activating Bad phosphorylation through the control of both kinases Cdk1 (show CDK1 Proteins) and JNK (show MAPK8 Proteins).
Findings reveal that XH2AX has a specific role in anterior neural formation of Xenopus, which is mediated through phosphorylation of XH2AX at Thr (show TRH Proteins)(16) by Chk1.
mechanism of Chk1 activation at the DNA replication checkpoint
During neurogenesis, cortical neurons became protected from S-phase Chk1 pathway activation by the DNA methyltransferase (show DNMT1 Proteins) Dnmt1 (show DNMT1 Proteins), and underwent cell death after S-phase progression.
work reveals that simulated microgravity promotes the apoptotic response through a combined modulation of the Uev1A/TICAM/TRAF (show TRAF1 Proteins)/NF-kappaB (show NFKB1 Proteins)-regulated apoptosis and the p53 (show TP53 Proteins)/PCNA (show PCNA Proteins)- and ATM (show ATM Proteins)/ATR-Chk1/2-controlled DNA-damage response pathways.
Chk1(-/-) MEFs exhibited the absence of double-strand breaks, yet cells showed delayed DNA damage recovery with pan-nuclear immunostaining pattern of Histone H2AX.
RAD9 (show RAD9A Proteins) has a prominent role in the ATR-Chk1 pathway that is necessary for successful formation of the damage-sensing complex and DNA damage checkpoint signaling.
Acute inactivation of E4F1 (show E4F1 Proteins) in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS (show ROS1 Proteins) production, energy stress, and inhibition of de novo pyrimidine synthesis
Altogether, our results classify E4F1 (show E4F1 Proteins) as a master regulator of CHK1 activity that ensures high fidelity of DNA replication, thus safeguarding genome stability.
Heterozygous loss of Chk1 in a Wnt (show WNT2 Proteins)-driven background resulted in an increase in DNA damage and apoptosis and accelerated both tumour development and progression.
PAR, supplied by PARP1, interacts with Chk1 via a novel PAR-binding regulatory (PbR) motif in Chk1, independent of ATR and its activity
ATM (show ATM Proteins) (pSer-1981)-Chk1 (pSer-345) cascade might have mediated G2/M cell cycle arrest to allowed time to facilitate sperm-derived DNA damage repair in mouse zygotes fertilized with oxygen-stressed sperm.
High level of phospho-Chk1 is associated with skin tumors.
The Chk1 directly phosphorylates eNOS (show NOS3 Proteins) Ser (show SIGLEC1 Proteins)(1179) in response to UV irradiation, which is dependent on Hsp90 (show HSP90 Proteins) interaction.
The protein encoded by this gene belongs to the Ser/Thr protein kinase family. It is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. This protein acts to integrate signals from ATM and ATR, two cell cycle proteins involved in DNA damage responses, that also associate with chromatin in meiotic prophase I. Phosphorylation of CDC25A protein phosphatase by this protein is required for cells to delay cell cycle progression in response to double-strand DNA breaks. Several alternatively spliced transcript variants have been found for this gene.
CHK1 checkpoint homolog
, Serine/threonine-protein kinase Chk1-like protein
, serine/threonine-protein kinase Chk1
, serine/threonine-protein kinase chk1
, Checkpoint, S. pombe, homolog of, 1
, cell cycle checkpoint kinase
, checkpoint kinase-1
, Chk1 checkpoint kinase
, checkpoint kinase 1 homolog
, rad27 homolog
, integral membrane protein 1