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High mobility group A1 (HMGA1) has been identified to play a role in tumour progression but its involvement in anti-tumour immunity of esophagael squamous cell carcinoma (ESCC) remains unclear. Here the authors report that the inhibition of STING-mediated anti-tumour immunity by HMGA1 results in promotion of ESCC tumorigenesis.

Intracellular copper concentration has been linked to cell proliferation. Here, the authors demonstrate that copper binding to both Cyclin-dependent kinase 1 (CDK1) and CCNB1 is essential for activating CDK1 and promoting the G2/M transition in the cell cycle.

Aberrant expression of the human hexokinase HKDC1 has been observed in patients with cancer. Here the authors report that HKDC1 expression is associated with hepatocellular carcinoma progression and PD-L1 mediated immune evasion.

Cells actively sense external and internal signals to stay quiescent or proliferate, and this trigger relies on being in a reversible primed G1 state of partial retinoblastoma inactivation and E2F activation.

Cyclin-dependent kinases (CDK4/6) play a crucial role in initiating cell growth. Here, Zhang et al. unveil a mechanism that bypasses CDK4/6, shedding light on an alternative pathway of cell-cycle initiation and quiescence maintenance.

Two classes of enzyme — cyclin-dependent kinases (CDK) and Dbf4-dependent kinase (DDK) — facilitate the initiation of DNA replication in eukaryotes. It is now shown that, when DNA damage is sensed, another kinase, Rad53, halts the firing of late replication origins by inhibiting both the CDK and the DDK pathways. Rad53 acts on DDK directly by inhibiting Dbf4, whereas the CDK pathway is blocked by Rad53-mediated phosphorylation of the downstream CDK substrate Sld3.

DNA damage or replication stress induces the activation of checkpoint kinases, pausing the cell cycle so that DNA repair can take place; checkpoint activation must be regulated to prevent the cell-cycle arrest from persisting after damage is repaired, and now the Slx4–Rtt107 complex is shown to regulate checkpoint kinase activity by directly monitoring DNA-damage signalling.

Kinase regulatory pathways are used in eukaryotic DNA replication to facilitate coordination with other processes during cell division cycles and response to environmental cues. The Dbf4–Cdc7 kinase (DDK) is one of at least two cell-cycle-regulated protein kinase systems essential for initiation of DNA replication. DDK is now shown to relieve the inhibitory activity of the amino-terminal ___domain of the replicative helicase Mcm4, thus promoting S phase.

The ends of chromosomes, known as telomeres, look like ends generated by double-strand breaks, but if treated as such the DNA damage repair system would initiate a checkpoint response and cause telomere–telomere fusions. These authors show that telomeres lack two types of histone modification that are required for recruitment of Crb2^b53BP1, without which the checkpoint cannot be activated even if other DNA damage response proteins are recruited to a Taz1-deficient telomere.

It is unknown how the kinetochore fibrous corona is disassembled. Here, the authors reveal that Aurora A and B kinases-mediated phosphorylation activates CENP-E, which is essential to prevent the premature removal of corona proteins by dynein.

We uncover the mechanism underlying the restriction point phenomenon, suggest a role for cyclin-dependent kinase 4 and 6 activity in S and G2 phases, and explain the behaviour of cells following loss of mitogen signalling.

NKR-P1 is an inhibitory receptor on the surface of natural killer cells, and its engagement with the ligand LLT1 on activated monocytes and B cells triggers NK cell self-tolerance and other immunological processes. Here authors set up a comprehensive, structure-based model of NKR-P1-LLT1 interaction that involves NKR-P1 homodimer formation and subsequent bridging of two LLT1 molecules.

The functional role of airway basal cells has not been comprehensively studied in idiopathic pulmonary fibrosis (IPF). Here, the authors show that airway basal cells of IPF patients display a distinct phenotype, are profibrotic if transplanted to mice and that fibrosis can be ameliorated by Src iinhibitors.

The microtubule plus-end tracking protein Tip1 regulates microtubule dynamics and polar growth in fission yeast. Here the authors link the ubiquitination of Tip1 by ubiquitin ligase Dma1 to polarized growth inhibition upon DNA replication stress.

How normal cells proliferate without CDK4 and CDK6, two cancer-driving kinases, remains unclear. Here, the authors show that without CDK4/6 activity, cells start the cell cycle with a different signaling order and commitment point, revealing unexpected flexibility in cell-cycle entry mechanisms.

The vascular endothelium contributes to metabolic regulation, however, the underlying mechanisms are not fully understood. Here the authors show that endothelial low-density lipoprotein receptor-related protein 1 regulates glucose homeostasis via osteocalcin expression.

The transcription factor RUNX3 plays a key role in the restriction point of cell cycle. Here the authors showed that RUNX3 binds and opens chromatin structure of restriction point associated genes, by sequential recruitment of chromatin remodeling complex, transcription complex and cell cycle regulators.

DNA damage triggers checkpoint signalling mechanisms. Here the authors reveal differential phosphorylation of targets of the Mec1-Ddc2 checkpoint kinase by analyzing the effect of quantitatively different ssDNA signals.

Spindle assembly checkpoint controls anaphase onset and guarantees appropriate chromosome segregation. Here, the authors report that dynamin-related protein 1 is recruited to kinetochores by CENP-F to regulate metaphase-to-anaphase transition by controlling APC/C activity in mouse oocyte meiosis

DNA replication stress promotes genome instability and cell death. Here Fugger et al.describe how FBH1, via its helicase activity, is required to eliminate cells with excessive DNA replication stress, through the generation of MUS81-induced DNA double-strand breaks.

Cyclin B-dependent kinase 1, the M-phase-promoting factor, is precisely activated and inactivated to control mitosis. In this study, Fcp1—the RNA polymerase II-carboxy-terminal ___domain phosphatase—is identified as a phosphatase required to inactivate the M-phase-promoting factor and promote mitosis exit.

Mitotic exit is controlled by a cell division checkpoint that prevents premature degradation of cyclin B by the anaphase-promoting complex. Saurinet al. show that Aurora B directly regulates timely establishment of this checkpoint by facilitating activation of Mps1 kinase at unattached kinetochores.

Effective therapeutic options are still needed in neuroblastoma treatment. Here, the authors, through a comprehensive proteomics analysis, identify ATR as a potential therapeutic target of neuroblastoma and demonstrate the efficacy of the ATR inhibitor BAY1895344 in combination with the ALK tyrosine kinase inhibitor lorlatinib.

The nucleus is a mechanically stiff organelle of the cell and the DNA damage response protein ATR can localize to the nuclear envelope upon mechanical stress. Here, the authors show that ATR may contribute to the integrity of the nuclear envelope and may play a role in cell migration.

The relationship between DNA damage response (DDR) and regulation of the tolerance to glucose restriction is currently unclear. Here the authors reveal that maintaining a physiological level of histones by Rad53-Spt21 is necessary for glucose tolerance via multiple parallel pathways, including derepression of subtelomeric genes and acetyl-coA regulation by histone acetylation.

The tumour suppressor ARF regulates p53 levels; however, in contrast to p53, ARF has not been implicated in the response to DNA damage. In this study, Carlos et al.show that single-stranded DNA formed in BRCA2-null cells triggers a DNA damage response leading to the activation of ARF and senescence.

The mitotic checkpoint complex (MCC) inhibits the anaphase-promoting complex (APC/C) bound to Cdc20 in response to spindle defects. Here, the authors show that Bub1-Plk1-mediated phosphorylation of Cdc20 constitutes a parallel, non-redundant APC/C-inhibitory mechanism in addition to MCC activity.

Kinetochores that fail to form bipolar attachments to the mitotic spindle delay chromosome segregation by BubR1 mediated inhibition of Cdc20. Lischetti et al.show that BubR1 recruits Cdc20 to the kinetochore via a ___domain that mediates both checkpoint activation and silencing.

Borealin is a subunit of the chromosomal passenger complex that prevents premature mitosis before spindle assembly is complete. Bekier et al.show that Borealin mediates recruitment of this complex to both kinetochores and centromeres via distinct mechanisms, both of which depend on Borealin dimerization.

The mitotic exit network (MEN) triggers mitotic exit and can be blocked by the spindle position checkpoint (SPOC). Here the authors show that SPOC kinase Kin4 counterbalances MEN activation by the Cdc fourteen early anaphase release (FEAR) network in the mother cell and that in the absence of FEAR mitotic exit requires daughter cell-confined factors.

KAT5 tyrosine phosphorylation, mediated by the tyrosine kinase c-Abl, increases after DNA damage, promoting KAT5 binding to histone H3K9me3, which triggers KAT5-mediated acetylation of the ATM kinase; this promotes the activation of the DNA damage checkpoint and cell survival.

The spindle assembly checkpoint (SAC) depends on the recruitment of specific protein complexes to the kinetochore. Here Zhang et al. show that Bub1 recruits the RZZ complex and BubR1 to the kinetochore, and loss of the BubR1 binding sequence enhances checkpoint activity suggesting both SAC activating and silencing roles.

Resistance to chemotherapy occurs in many ovarian cancer cases. Here, the authors show that mir-424(322) expression restores the sensitivity of ovarian cancer cells to chemotherapy by blocking the PD-L1 immune checkpoint, and find that combining immunotherapy and chemotherapy has a synergistic effect.

Bub1 kinase phosphorylates histone H2A-T120 at the centromere to recruit shugoshin proteins and promote sister chromatid cohesion during mitosis. Here the authors show that Bub1 autophosphorylation on T589 influences Bub1 dynamics at the kinetochore and restricts H2A-T120 phosphorylation to centromeres.

DNA double strand breaks can be repaired by homology-independent or homology-directed mechanisms. The choice between these pathways is a key event for genomic stability maintenance. Here the authors identify and characterize AUNIP, as a factor involved in tilting the balance towards homology repair.

ATR kinase activity is essential for slowing replication forks and preventing DNA replication in cells with DNA damage. Here the authors show that ATR inhibition leads to Cdc7 phosphorylation of GINS, leading to origin firing.

Checkpoint kinases control cell cycle progression via the regulation of many key regulators. Here the authors demonstrate how HDAC1 and HDAC2 modulate checkpoint kinase signalling via the suppression of PR130, a regulatory subunit of the trimeric serine/threonine phosphatase 2.

The plant DNA damage response ensures genomic stability by controlling interconnected networks of DNA repair and cell division proteins. Decoding these networks offers potential solutions to the challenges of climate-related stress and food security.

The kinase MPS1 is a conserved and essential component of the spindle assembly checkpoint (SAC), but its relevant substrate in this context has remained uncertain. Watanabe and colleagues now show that, in fission yeast and human cells, MPS1 (Mph1 in fission yeast) phosphorylates the kinetochore protein KNL1 (Spc7), leading to kinetochore recruitment of BUB1, an event required for SAC activation.

Targeting Mad1 to kinetochores reveals that Mad1 localization is sufficient to induce mitotic-checkpoint-dependent arrest, and that Aurora B, Mps1 and BubR1 are required for checkpoint maintenance.

Isoform B of the chromatin-binding protein Brd4 acts to suppress DNA damage response signalling.

The spindle assembly checkpoint (SAC) arrests cells in metaphase until all chromosomes are attached to the spindle. Dick and Gerlich used laser microsurgery to detach individual chromosomes, revealing that the SAC does not have a switch-like response — instead, SAC strength depends on the number of unattached chromosomes.