ABSTRACT
This article is the result of 700 interviews that have taken place during the past three years in the «Espace Proches¼ in Lausanne, a place devoted to home caregivers. It attempts to describe the reality of relatives and highlight the specific difficulties they encounter in the different roles they adopt or are given by their surroundings in the face of a progressive disease. It offers suggestions to the physicians of this population at risk on how to better support them in their physical and psychological burden.
Cet article est le fruit de 700 entretiens menés ces trois dernières années au sein de l'«Espace Proches¼ à Lausanne, un lieu consacré à l'accueil des aidants naturels. Il tente de décrire la réalité des proches et de mettre en évidence leurs difficultés spécifiques dans les différents rôles qu'ils assument où qui leurs sont attribués par l'entourage lors d'une maladie évolutive. Il propose au médecin traitant des pistes permettant à ce dernier de mieux soutenir cette population à risque en raison de la charge physique et psychologique qu'elle subit.
Subject(s)
Caregivers/psychology , Family Practice , Palliative Care/methods , Palliative Care/psychology , Terminal Care/psychology , Cost of Illness , Humans , Physician's Role , Professional-Family Relations , Social Support , Switzerland , Terminal Care/methodsABSTRACT
DNA damage leads to activation of several mechanisms such as DNA repair and cell-cycle checkpoints. It is evident that these different cellular mechanisms have to be finely co-ordinated. Growing evidence suggests that the Rad9/Rad1/Hus1 cell-cycle checkpoint complex (9-1-1 complex), which is recruited to DNA lesion upon DNA damage, plays a major role in DNA repair. This complex has been shown to interact with and stimulate several proteins involved in long-patch base excision repair. On the other hand, the well-characterised DNA clamp-proliferating cell nuclear antigen (PCNA) also interacts with and stimulates several of these factors. In this work, we compared the effects of the 9-1-1 complex and PCNA on flap endonuclease 1 (Fen1). Our data suggest that PCNA and the 9-1-1 complex can independently bind to and activate Fen1. Finally, acetylation of Fen1 by p300-HAT abolished the stimulatory effect of the 9-1-1 complex but not that of PCNA, suggesting a possible mechanism of regulation of this important repair pathway.
Subject(s)
Cell Cycle Proteins/physiology , DNA Repair , Flap Endonucleases/metabolism , Proliferating Cell Nuclear Antigen/physiology , Cell Cycle Proteins/metabolism , Cloning, Molecular , DNA Damage , Exonucleases/physiology , Histone Acetyltransferases/metabolism , Humans , Multiprotein Complexes/physiology , Transcription Factors/metabolism , p300-CBP Transcription FactorsABSTRACT
We describe a novel regulatory mechanism for DNA polymerase beta (Polbeta), a protein involved in DNA base excision repair (BER). Polbeta colocalized in vivo and formed a complex with the transcriptional coactivator p300. p300 interacted with Polbeta through distinct domains and acetylated Polbeta in vitro. Polbeta acetylation was furthermore observed in vivo. Lysine 72 of Polbeta was identified as the main target for acetylation by p300. Interestingly, acetylated Polbeta showed a severely reduced ability to participate in a reconstituted BER assay. This was due to an impairment of the dRP-lyase activity of Polbeta. Acetylation of Polbeta thus acts as an intranuclear regulatory mechanism and implies that p300 plays a critical regulatory role in BER.
