NATIONAL INSTITUTES OF HEALTH
In some cancers, chromosomes are broken apart and stitched back together, resulting in tens to hundreds of spontaneous genomic rearrangements, contravening the model of slowly accumulating point mutations and more subtle chromosome rearrangements. The process, dubbed "chromothripsis," occurs in at least 2-3 percent of all cancers, across many subtypes, and is present in 25 percent of bone cancers.
P.J. Stephens, et al., "Massive genomic rearrangement acquired in a single catastrophic event during cancer development," Cell, 144:27-40, 2011.
Getting chromosome segregation right during mitosis is crucial to accurate cell division, and this delicate orchestration depends on the proper formation and localization of the kinetochore, a protein complex normally formed in the cell's centromere. New research shows that two DNA-binding proteins, CENP-C and CENP-T, known to drive vertebrate kinetochore formation can direct its assembly even outside the centromere.
K.E. Gascoigne KE, et al., "Induced ectopic kinetochore assembly bypasses the requirement for CENP-A nucleosomes," Cell, 145:410-22, 2011.
Hormone treatment is a core therapy for breast cancer, but many patients are resistant to the drugs, which target estrogen receptor-a. A ubiquitin-binding protein called CUEDC2 seems to be central to conferring resistance to endocrine drugs like tamoxifen.
X. Pan, et al., "Elevated expression of CUEDC2 protein confers endocrine resistance in breast cancer," Nat Med., 17:708-14, 2011.
The DNA repair protein cyclin D1 is a hallmark of many cancers, and now an interactome analysis of several tumor types is revealing its function by bringing to light many of its molecular binding partners, such as the recombinase RAD51.
S. Jirawatnotai, et al., "A function for cyclin D1 in DNA repair uncovered by protein interactome analyses in human cancers," Nature, 474:230-4, 2011.
The protein Cdc45 plays a key role in eukaryotic DNA replication, but its precise enzymatic activity has remained a mystery. Using a bioinformatic approach, researchers determine that Cdc45 is related to the prokaryotic homologous recombination and mismatch repair protein RecJ, suggesting Cdc45 may have a similar function.
L. Sanchez-Pulido and C.P. Ponting, "Cdc45: The Missing RecJ Ortholog in Eukaryotes?" Bioinformatics, Jun 8. [Epub ahead of print], 2011.
An important cell cycle regulator called cyclin-dependent kinase 1 (Cdk1) interacts with many different types of cyclin, and now it appears that it's able to order specific events in the cell cycle by changing its substrate specificity to associate with different cyclins.
M. Kõivomägi et al., "Dynamics of Cdk1 Substrate Specificity during the Cell Cycle," Mol. Cell, 42:610-23, 2011.
Cells are able to sense the degree to which they need to condense chromatin during mitosis so that DNA segregates properly between daughter cells. When the longest chromosomes in yeast cells were made 45 percent longer, greater compaction occurred in anaphase to compensate and cells remained viable.
G. Neurohr, et al., "A midzone-based ruler adjusts chromosome compaction to anaphase spindle length," Science, 332:465-8, 2011.
The F1000 Top 7 is a snapshot of the highest ranked articles from a 30-day period on Faculty of 1000 in cancer biology and related areas, as calculated on July 5, 2011. Faculty Members evaluate and rate the most important papers in their field. To see the latest rankings, search the database, and read daily evaluations, visit http://f1000.com.