Cell cycle

Cohesin release is required for sister chromatid resolution, but not for condensin-mediated compaction, at the onset of mitosis. Losada, A. et al. Genes Dev. 16, 3004–3016 (2002)

Cohesin and condensin are protein complexes that mediate sister-chromatid cohesion and condensation, respectively, in preparation for sister-chromatid separation. In metazoans, cohesin is released during prophase, which occurs at the same time as condensin association. Losada et al. now show that two mitotic kinases, aurora B and polo-like kinase Plx1, cooperate to dissociate cohesin from chromatin at the onset of mitosis, which is essential for sister-chromatid resolution, but not for condensin-mediated compaction.

DNA replication

An ACF1–ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin. Collins, N. et al. Nature Genet. 32, 627–632 (2002)

The mechanism that enables the DNA replication machinery to penetrate heterochromatin is poorly understood. However, Collins et al. now provide evidence that an ACF1–ISWI chromatin-remodelling complex is required for replication through highly condensed regions of chromatin. Depletion of ACF1 or the ISWI isoform SNF2H causes a delay in DNA replication in S phase. In addition, chemically decondensing the heterochromatin abolishes the requirement for ACF1 and SNF2H.

Development

Identification of a Wnt/Dvl/β-catenin→Pitx2 pathway mediating cell-type-specific proliferation during development. Kioussi, C. et al. Cell 111, 673–685 (2002)

This paper describes a cell-specific proliferation strategy during cardiac and pituitary development, which requires the tissue-restricted transcription factor Pitx2. Activation of the Wnt/Dvl/β-catenin signalling pathway results in the rapid induction of Pitx2, and the binding of Pitx2 to the promoter of growth-control genes, such as Cyclin D2, that act in G1. Pitx2 then recruits a series of coactivator complexes required for promoter stimulation in a temporal and growth-factor-specific manner.

Signal transduction

The protein kinase complement of the human genome. Manning, G. et al. Science 298, 1912–1918 (2002)

Most protein kinases belong to a single superfamily, the members of which contain a eukaryotic protein kinase (ePK) catalytic domain. Manning et al. have now catalogued the protein kinase complement of the human genome (the 'kinome') and identified 478 ePKs and 40 'atypical' protein kinase genes. Among these 518 putative protein kinases, 71 have not been previously reported or described as kinases. Importantly, 244 kinases map to disease loci or cancer amplicons.