RESUMO
The RAD9-RAD1-HUS1 complex (9-1-1) is a eukaryotic DNA clamp with a crucial role at checkpoints for DNA damage. The ring-like structure of 9-1-1 is opened for loading onto 5' recessed DNA by the clamp loader RAD17 RFC-like complex (RAD17-RLC), in which the RAD17 subunit is responsible for specificity to 9-1-1. Loading of 9-1-1 is required for activation of the ATR-CHK1 checkpoint pathway and the activation is stimulated by a 9-1-1 interacting protein, RHINO, which interacts with 9-1-1 via a recently identified RAD1-binding motif. This discovery led to the hypothesis that other interacting proteins may contain a RAD1-binding motif as well. Here, we show that vertebrate RAD17 proteins also have a putative RAD1-binding motif in their N-terminal regions, and we report the crystal structure of human 9-1-1 bound to a human RAD17 peptide incorporating the motif at 2.1 Å resolution. Our structure confirms that the N-terminal region of RAD17 binds to the RAD1 subunit of 9-1-1 via specific interactions. Furthermore, we show that the RAD1-binding motif of RHINO disturbs the interaction of the N-terminal region of RAD17 with 9-1-1. Our results provide deeper understanding of how RAD17-RLC specifically recognizes 9-1-1 and imply that RHINO has a functional role in 9-1-1 loading/unloading and checkpoint activation.
Assuntos
Proteínas de Transporte , Proteínas de Ciclo Celular , Exonucleases , Humanos , Proteínas de Transporte/metabolismo , Proteínas de Ciclo Celular/metabolismo , DNA/metabolismo , Dano ao DNA , Proteínas de Ligação a DNA/metabolismo , Exonucleases/metabolismoRESUMO
The appearance and symmetry of the auricle is crucial for the maintenance of facial cosmetic harmony. The earlobe is considered to be an important attribute of beauty in most cultures, and earlobe decoration with color or earring is a common practice in many societies. A reconstructive technique for congenital or acquired deformity of the earlobe is described. In addition, the postauricular chondrocutaneous flap is very convenient for reconstruction of various auricular parts.
Assuntos
Deformidades Adquiridas da Orelha/cirurgia , Orelha Externa/anormalidades , Orelha Externa/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Adulto , Criança , Feminino , HumanosRESUMO
Nonsurgical treatment does not always correct all auricular deformities. However, we believe that all types of deformities can be treated if the gradual and continuous correction is made. Therefore, it is recommended that nonsurgical treatment should be tried first, even in older children. Even if the correction with the splint is not satisfactory, the improved form with the splint will make it easier to obtain a good, delicate form by surgery at a later stage.