Phosphorylation of TIP60 Suppresses 53BP1 Localization at DNA Damage Sites.

A proper balance between the repair of DNA double-strand breaks (DSBs) by homologous recombination and nonhomologous end joining is critical for maintaining genome integrity and preventing tumorigenesis. This balance is regulated and fine-tuned by a variety of factors, including cell cycle and the chromatin environment. The histone acetyltransferase TIP60 was previously shown to suppress pathological end joining and promote homologous recombination.

Actin polymerization controls cilia-mediated signaling.

Primary cilia are polarized organelles that allow detection of extracellular signals such as Hedgehog (Hh). How the cytoskeleton supporting the cilium generates and maintains a structure that finely tunes cellular response remains unclear. Here, we find that regulation of actin polymerization controls primary cilia and Hh signaling.

Chromatin yo-yo: expansion and condensation during DNA repair.

DNA double-strand breaks are repaired by nonhomologous end-joining (NHEJ) and homologous recombination (HR). Disrupting the balance between these pathways results in toxic chromosomal rearrangements. Several recent studies are revealing that dynamic changes in chromatin conformation can regulate DNA repair pathway choice both spatially and temporally.

GLI activation by atypical protein kinase C ι/λ regulates the growth of basal cell carcinomas.

Growth of basal cell carcinomas (BCCs) requires high levels of hedgehog (HH) signalling through the transcription factor GLI. Although inhibitors of membrane protein smoothened (SMO) effectively suppress HH signalling, early tumour resistance illustrates the need for additional downstream targets for therapy. Here we identify atypical protein kinase C ι/λ (aPKC-ι/λ) as a novel GLI regulator in mammals.

Links between genome integrity and BRCA1 tumor suppression.

BRCA1 and BRCA2 are two major breast and ovarian cancer susceptibility genes. BRCA1 was the first discovered and has been a focus of research for these cancers. BRCA1 mediates tumor suppression in part through pleiotropic interactions with a network of DNA repair proteins on chromatin.

MIM and cortactin antagonism regulates ciliogenesis and hedgehog signaling.

The primary cilium is critical for transducing Sonic hedgehog (Shh) signaling, but the mechanisms of its transient assembly are poorly understood. Previously we showed that the actin regulatory protein Missing-in-Metastasis (MIM) regulates Shh signaling, but the nature of MIM's role was unknown. Here we show that MIM is required at the basal body of mesenchymal cells for cilia maintenance, Shh responsiveness, and de novo hair follicle formation.