Volume 11 Issue 8, August 2009

In Caernorhabditis elegans, homologue pairing is mediated by specialized regions near one end of each chromosome in conjunction with zinc finger (ZnF)-bearing proteins. Families of repeated sequences that are enriched within these regions have now been identified. By recruiting their cognate ZnF-bearing proteins, these regions promote pairing and synapsis.

Translation of localized mRNAs is an important mechanism for controlling spatially discrete cellular processes. The polarity protein Par-3 is locally translated in axons in response to factors such as NGF and netrin-1, and this increased expression is necessary for factor-stimulated axonal outgrowth.

Senescent cells alter their microenvironment by secreting a growing collection of factors, a phenomenon termed the senescence-associated secretory phenotype (SASP). Cellular senescence is often the result of nuclear DNA damage fuelling a chronic DNA damage response (DDR). Upstream elements of the DDR cascade are necessary for full blown SASP, and additional crosstalk occurs between the DDR and cytokine secretion.

Non-chromatin associated histones are unstable in budding yeast. Tyrosine phosphorylation of histone H3 followed by subsequent ubiquitylation by the ubiquitin conjugating enzymes Ubc4 and Ubc5 and the ubiquitin ligase Tom1 triggers H3 degradation.

Pairing centres are specialized regions on worm chromosomes that mediate homologous pairing during meiosis. Sequence motifs that recruit proteins involved in pairing have been identified and they are sufficient for chromosome synapsis and segregation during meiosis.

TGF-β mediates epithelial-mesenchymal transitions (EMT) during tumorigenesis but the molecular mechanisms driving this effect have been unclear. The transcriptional repressor SNAIL1 and the downstream effector of TGF-β SMAD3/4 cooperate to repress gene expression during TGF-β-mediated EMT.

Notch1 inhibits cardiac progenitor cell expansion by preventing the accumulation of phosphorylated β-catenin, which normally promotes their proliferation. In a feedback loop, Notch1 positively regulates the expression of cardiac transcription factors to induce progenitor cell differentiation, whereas β-catenin has the reverse effect.

Mice that lack the fission mitochondrial GTPase Drp1, are shown to die during embryonic development. Although Drp1 is not required for apoptosis, the absence of Drp1 leads to neuronal and synaptic defects due to a failure of elongated mitochondria to reach distal parts of axons.

Pin1 regulates protein degradation and is now shown to control the ubiquitylation status of its targets. In yeast, Pin1 decreases the ubiquitylation of the transcription factor Spt23 to activate it, while low Pin1 levels increase its degradation. Similarly, inhibition of Pin1 in mammalian cells increases p53 ubiquitylation and nuclear degradation.

Persistent DNA damage activation and oncogene-induced senescence stimulate secretion of the inflammatory cytokine IL-6, which is mediated by the damage-response pathway including ATM, NBS1 and CHK2. Tumours with an activated DNA damage response show elevated IL-6 and invasiveness.

Cells with a single short telomere and lacking telomerase mount a damage response consisting of recruitment of DNA damage checkpoint proteins, Cdc13, RPA and Rad52, many generations before senescence and in addition show tethering of the short telomere to the nuclear pore complex.

Cells with a single short telomere and lacking telomerase continue to divide until they activate a Mec1/ATR-dependent checkpoint, causing senescence.

The tumour suppressor protein VHL, which is inactivated in hereditary and sporadic forms of renal cell carcinoma, is found at the mitotic spindle in mammalian cells. VHL inactivation leads to unstable astral microtubules and spindle misorientation as well as to reduced levels of Mad2, resulting in spindle checkpoint weakening and genomic instability.

Oculo-facio-cardio-dental (OFCD) syndrome is associated with mutations in the co-repressor BCOR. Mesenchymal stem cells from OFCD patients show higher osteo- and dentinogenic potential, partly due to defects in AP-2a expression. BCOR mutations impair the recruitment of the histone demethylase JHDM1B to the AP-2a promoter.

The chromatin remodeller NoRC silences rDNA by establishing heterochromatin. TIP5, a subunit of NoRC is acetylated by MOF and deacetylated by SIRT1 at Lys 633. Acetylation decreases TIP5 binding to rDNA promoter-associated RNA, leading to altered heterochromatin formation. TIP5 acetylation can be modified by changes in metabolism.

The Cdk4–pRb–E2F1 pathway is shown to have a role in insulin secretion in b cells by controlling the expression of a subunit of the K+ATP channel through E2F1 binding to its promoter.

During neuronal development, the axonal growth rate is regulated in conjunction with pathfinding. Stimulation of localized mRNA translation of the polarity protein PAR3 by neural growth factor (NGF) and netrin-1 is now shown to be required for axonal outgrowth.

MicroRNAs are frequently expressed in clusters, which often prevent the attribution of an individual microRNA to a specific function. Single overexpression of miR17, a microRNA belonging to a six-microRNA cluster, shows it controls heart, spleen and liver development by targeting fibronectin.

The actin cytoskleteon is essential for endocytosis in budding yeast but it is less significant in mammalian cells. Actin is shown to be required during plasma membrane invagination in yeast endocytosis due to the turgor pressure that is characteristic of yeast cells