Abstract：
:The concept of 'BRCAness' defines the pathogenesis and vulnerability of multiple cancers. The canonical definition of BRCAness is a defect in homologous recombination repair, mimicking BRCA1 or BRCA2 loss. In turn, BRCA-deficient cells utilize error-prone DNA-repair pathways, causing increased genomic instability, which may be responsible for their sensitivity to DNA damaging agents and poly-(ADP)-ribose polymerase inhibitors (PARPis). However, recent work has expanded the mechanistic basis of BRCAness, to include defects in replication fork protection (RFP). Here, we broaden the definition of BRCAness to include RFP and regulatory mechanisms that cause synthetic lethality with PARPis. We highlight these recent discoveries, which include mechanisms of RFP regulation, DNA damage checkpoint proteins, as well as kinases that regulate BRCA1/2 function. Importantly, many of these emerging mechanisms may be targeted for inhibition with small molecule inhibitors, thus inducing BRCAness in a much larger subset of BRCA-proficient tumors, with significant translational potential.
journal_name
Trends Cell Bioljournal_title
Trends in cell biologyauthors
Byrum AK,Vindigni A,Mosammaparast Ndoi
10.1016/j.tcb.2019.06.005subject
Has Abstractpub_date
2019-09-01 00:00:00pages
740-751issue
9eissn
0962-8924issn
1879-3088pii
S0962-8924(19)30104-7journal_volume
29pub_type
杂志文章,评审abstract：:The anaphase-promoting complex/cyclosome (APC/C) is an evolutionarily conserved ubiquitin ligase that controls cell cycle progression through spatiotemporally regulated proteolysis. Although recent studies revealed its postmitotic function, our knowledge of the role of APC/C beyond cell cycle regulation in the biology...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2019.03.001
更新日期：2019-07-01 00:00:00
abstract：:The actin-depolymerizing factor (ADF)/cofilins are a family of essential actin regulatory proteins, ubiquitous among eukaryotes, that enhance the turnover of actin by regulating the rate constants of polymerization and depolymerization at filament ends, changing the twist of the filament and severing actin filaments. ...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/s0962-8924(99)01619-0
更新日期：1999-09-01 00:00:00
abstract：:Ciliary movement is powered by axonemal dynein. This article considers how a signal transduction cascade initiated at the cell membrane may activate outer dynein arms to change the velocity of microtubule sliding and the swimming speed of ciliated cells. For Paramecium, a critical event in the cascade is the cAMP-depe...
journal_title：Trends in cell biology
pub_type： 杂志文章
doi：10.1016/0962-8924(93)90092-f
更新日期：1993-11-01 00:00:00
abstract：:Structural plasticity of excitatory synapses is a vital component of neuronal development, synaptic plasticity and behavior, and its malfunction underlies many neurodevelopmental and psychiatric disorders. However, the molecular mechanisms that control dendritic spine morphogenesis have only recently emerged. We summa...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2008.07.002
更新日期：2008-09-01 00:00:00
abstract：:After nearly four decades of investigation, the dynein motor is finally on the verge of revealing its inner secrets. This multisubunit ATPase participates in several important microtubule-based motilities in eukaryotic cells. Numerous recent articles have advanced the understanding of the dynein motor substructure and...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2004.09.013
更新日期：2004-11-01 00:00:00
abstract：:The GINS complex is the most recently identified component of the eukaryotic DNA replication machinery and is required both for the initiation of chromosome replication and also for the normal progression of DNA replication forks. Several recent studies suggest that GINS associates at replication forks with the MCM he...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2007.04.002
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abstract：:Acetate and the related metabolism of acetyl-coenzyme A (acetyl-CoA) confer numerous metabolic functions, including energy production, lipid synthesis, and protein acetylation. Despite its importance as a nutrient for cellular metabolism, its source has been unclear. Recent studies have provided evidence to support th...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2019.05.005
更新日期：2019-09-01 00:00:00
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journal_title：Trends in cell biology
pub_type： 评论,杂志文章
doi：10.1016/j.tcb.2017.12.003
更新日期：2018-03-01 00:00:00
abstract：:The E2F family of transcriptional regulators sits at the center of cell cycle gene expression and plays vital roles in normal and cancer cell cycles. Whereas control of E2Fs by the retinoblastoma family of proteins is well established, much less is known about their regulation by ubiquitin pathways. Recent studies pla...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2020.05.002
更新日期：2020-08-01 00:00:00
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journal_title：Trends in cell biology
pub_type： 杂志文章
doi：10.1016/j.tcb.2016.04.008
更新日期：2016-07-01 00:00:00
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journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2020.11.001
更新日期：2021-02-01 00:00:00
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journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2018.06.008
更新日期：2018-11-01 00:00:00
abstract：:Bidirectional microtubule-dependent organelle transport in melanophores is regulated by cAMP through organelle-bound protein kinase A (PKA); however, the mechanisms responsible for this regulation are unknown. A recent study by Gelfand and colleagues demonstrates that, in addition to PKA, transport is regulated by the...
journal_title：Trends in cell biology
pub_type： 杂志文章
doi：10.1016/j.tcb.2005.06.002
更新日期：2005-08-01 00:00:00
abstract：:The light-sensitive outer segment organelle of the vertebrate photoreceptor cell is a modified cilium filled with hundreds of flattened 'disc' membranes that provide vast light-absorbing surfaces. The outer segment is constantly renewed with new discs added at its base every day. This continuous process is essential f...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2020.08.005
更新日期：2020-11-01 00:00:00
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journal_title：Trends in cell biology
pub_type： 杂志文章
doi：10.1016/0962-8924(94)90075-2
更新日期：1994-10-01 00:00:00
abstract：:Cellular membranes differ in their molecular organisation, shape, and dynamics. Knowing how these properties of membrane architecture relate to the presence and function of specific membrane components is fundamental for understanding membrane-associated cellular processes. Correlative light and electron microscopy (C...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2020.04.003
更新日期：2020-07-01 00:00:00
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journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/s0962-8924(03)00057-6
更新日期：2003-05-01 00:00:00
abstract：:DNA double-strand breaks (DSBs) are major threats to the genomic integrity of cells. If not taken care of properly, they can cause chromosome fragmentation, loss and translocation, possibly resulting in carcinogenesis. Upon DSB formation, cell-cycle checkpoints are triggered and multiple DSB repair pathways can be act...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/s0962-8924(98)01383-x
更新日期：1998-12-01 00:00:00
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journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2006.04.007
更新日期：2006-06-01 00:00:00
abstract：:Fibroblasts are found in most tissues, yet they remain poorly characterised. Different fibroblast subpopulations with distinct functions have been identified in the skin. This functional heterogeneity reflects the varied fibroblast lineages that arise from a common embryonic precursor. In addition to autocrine signals...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2014.10.001
更新日期：2015-02-01 00:00:00
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journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2004.07.009
更新日期：2004-08-01 00:00:00
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journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2018.02.006
更新日期：2018-06-01 00:00:00
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journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2012.03.003
更新日期：2012-06-01 00:00:00
abstract：:The regulation of endothelial cell contacts is of central importance for the barrier function of the blood vessel wall and for the control of leukocyte extravasation. In addition, the plasticity of endothelial cell contacts is regulated during angiogenesis by growth factors, such as vascular endothelial growth factor ...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2008.10.001
更新日期：2009-01-01 00:00:00
abstract：:Aggrecan is a large and highly complex macromolecule, uniquely structured to fill space in the extracellular matrix (ECM) of cartilage. Lethal chondrodystrophies resulting from mutations in the structural gene for aggrecan demonstrate the serious consequences of the absence of aggrecan. Other chondrodystrophies are te...
journal_title：Trends in cell biology
pub_type： 杂志文章
doi：10.1016/s0962-8924(00)89115-1
更新日期：1995-12-01 00:00:00
abstract：:Research performed over the past decade has transformed apoptosis from a distinctive form of cell death known only by its characteristic morphology and genomic destruction to an increasingly well understood cellular disassembly pathway remarkable for its complex and multifaceted regulation. Here, we summarize current ...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/s0962-8924(01)02173-0
更新日期：2001-12-01 00:00:00
abstract：:Members of the myosin-I family of molecular motors are expressed in many eukaryotes, where they are involved in a multitude of critical processes. Humans express eight distinct members of the myosin-I family, making it the second largest family of myosins expressed in humans. Despite the high degree of sequence conser...
journal_title：Trends in cell biology
pub_type： 杂志文章,评审
doi：10.1016/j.tcb.2012.10.008
更新日期：2013-02-01 00:00:00
abstract：:Proteins of the cyclophilin family display two intriguing properties. On the one hand, they are the intracellular receptors for the immunosuppressive drug cyclosporin A (CsA); on the other hand, they function in vitro as enzymes that catalyse slow steps in protein folding. A dissection of the role of CsA in mediating ...
journal_title：Trends in cell biology
pub_type： 杂志文章
doi：10.1016/0962-8924(92)90200-7
更新日期：1992-09-01 00:00:00
abstract：:Plant seeds store nitrogen by accumulating storage proteins in protein bodies within various compartments of the endomembrane system. The prolamin storage proteins of some cereal species are normally retained and assembled into protein bodies within the ER. Yet, these proteins lack a C-terminal KDEL/HDEL signal, sugge...
journal_title：Trends in cell biology
pub_type： 杂志文章
doi：10.1016/0962-8924(93)90033-w
更新日期：1993-12-01 00:00:00
abstract：:Diverse biological and developmental functions are mediated by signalling through the epidermal growth factor (EGF) receptor. In flies, many different mechanisms are used to control and restrict EGF-R signalling, including ligand processing, ligand variety (an inhibitor as well as activators), transcription and perhap...
journal_title：Trends in cell biology
pub_type： 杂志文章
doi：10.1016/S0962-8924(97)01143-4
更新日期：1997-11-01 00:00:00
