Homology-directed repair (HDR) is a mechanism in cells to repair double-strand DNA lesions. The most common form of HDR is homologous recombination. The HDR mechanism can only be used by the cell when there is a homologous piece of DNA present in the nucleus, mostly in G2 and S phase of the cell cycle. Other examples of homology-directed repair include single-strand annealing and breakage-induced replication. When the homologous DNA is absent, another process called non-homologous end joining (NHEJ) takes place instead.
HDR is important for suppressing the formation of cancer. HDR maintains genomic stability by repairing broken DNA strands; it is assumed to be error free because of the use of a template. When a double strand DNA lesion is repaired by NHEJ there is no validating DNA template present so it may result in a novel DNA strand formation with loss of information. A different nucleotide sequence in the DNA strand results in a different protein expressed in the cell. This protein error may cause processes in the cell to fail. For example, a receptor of the cell that can receive a signal to stop dividing may malfunction, so the cell ignores the signal and keeps dividing and can form a cancer. The importance of HDR can be seen from the fact that the mechanism is conserved throughout evolution. The HDR mechanism has also been found in more simple organisms, such as yeast.
The pathway of HDR has not been totally elucidated yet (March 2008). However, a number of experimental results point to the validity of certain models.
It is generally accepted that histone H2AX (noted as γH2AX) is phosphorylated within seconds after damage occurs. H2AX is phosphorylated throughout the area surrounding the damage, not only precisely at the break. Therefore, it has been suggested that γH2AX functions as an adhesive component for attracting proteins to the damaged location. Several research groups have suggested that the phosphorylation of H2AX is done by ATM and ATR in cooperation with MDC1.
Cette page est générée automatiquement et peut contenir des informations qui ne sont pas correctes, complètes, à jour ou pertinentes par rapport à votre recherche. Il en va de même pour toutes les autres pages de ce site. Veillez à vérifier les informations auprès des sources officielles de l'EPFL.
vignette|La jonction d'extrémités non homologues. La jonction d'extrémités non homologues (en anglais Non-Homologous End-Joining ou NHEJ) est un mécanisme de réparation de l'ADN qui permet de réparer des lésions provoquant des cassures double brin (CDB). C'est un mécanisme non-conservatif (contrairement par exemple à la réparation par recombinaison) c'est-à-dire qu'il ne restaure pas la séquence initiale de l'ADN; mais seulement la continuité de l'ADN endommagé par une cassure double brin.
thumb | 275px | alt=Schéma du chromosome 1 après recombinaison homologue | Figure 1. La recombinaison homologue peut produire de nouvelles combinaisons d'allèles entre les chromosomes parentaux, notamment lors de la méiose.La recombinaison homologue est un type de recombinaison génétique où les séquences de nucléotides sont échangées entre des molécules d'ADN identiques (homologues) ou similaires (Figure 1). Au sens large, la recombinaison homologue est un mécanisme ubiquitaire de réparation des cassures double-brins de l'ADN.
The course covers in detail molecular mechanisms of cancer development with emphasis on cell cycle control, genome stability, oncogenes and tumor suppressor genes.
Le but du cours est de fournir un aperçu général de la biologie des cellules et des organismes. Nous en discuterons dans le contexte de la vie des cellules et des organismes, en mettant l'accent sur l
Telomeres are nucleoprotein structures at the ends of linear chromosomes, being essential for the maintenance of genomic integrity. Telomeres have a unique structure which distinguishes chromosome termini from DNA damage sites. Shelterin complexes are the ...
EPFL2023
,
Solar disinfection (SODIS) was probed for its underlying mechanism. When Escherichia coli was exposed to UVA irradiation, the dominant solar fraction acting in SODIS process, cells exhibited a shoulder before death ensued. This profile resembles cell killi ...
PERGAMON-ELSEVIER SCIENCE LTD2022
, ,
Telomeres protect chromosome ends from nucleolytic degradation, uncontrolled recombination by DNA repair enzymes and checkpoint signaling, and they provide mechanisms for their maintenance by semiconservative DNA replication, telomerase and homologous reco ...