Title :

Non Random Distribution of DMD Deletion Breakpoints and Implication of Double Strand Breaks Repair and Replication Error Repair Mechanisms.

Author(s) :

Marey, Isabelle [Auteur]
Ben Yaou, Rabah [Auteur]
Deburgrave, Nathalie [Auteur]
Vasson, Aurelie [Auteur]
Nectoux, Juliette [Auteur]
Leturcq, France [Auteur]
Eymard, Bruno [Auteur]
Laforêt, Pascal [Auteur]
Béhin, Anthony [Auteur]
Stojkovic, Tanya [Auteur]
Mayer, Michele [Auteur]
Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 [CRIStAL]
Tiffreau, Vincent [Auteur]
Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 [URePSSS]
Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369
Desguerre, Isabelle [Auteur]
Boyer, François-Constant [Auteur]
Nadaj-Pakleza, Aleksandra [Auteur]
Ferrer, Xavier [Auteur]
Wahbi, Karim [Auteur]
Bécane, Henri-Marc [Auteur]
Claustres, Mireille [Auteur]
Chelly, Jamel [Auteur]
Cossee, Mireille [Auteur]

Journal title :

Journal of neuromuscular diseases

Abbreviated title :

J Neuromuscul Dis

Volume number :

3

Pages :

227-245

Publication date :

2016-05-27

ISSN :

2214-3602
2214-3599

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Dystrophinopathies are mostly caused by copy number variations, especially deletions, in the dystrophin gene (DMD). Despite the large size of the gene, deletions do not occur randomly but mainly in two hot spots, the main ...
Show more >Dystrophinopathies are mostly caused by copy number variations, especially deletions, in the dystrophin gene (DMD). Despite the large size of the gene, deletions do not occur randomly but mainly in two hot spots, the main one involving exons 45 to 55. The underlying mechanisms are complex and implicate two main mechanisms: Non-homologous end joining (NHEJ) and micro-homology mediated replication-dependent recombination (MMRDR). Our goals were to assess the distribution of intronic breakpoints (BPs) in the genomic sequence of the main hot spot of deletions within DMD gene and to search for specific sequences at or near to BPs that might promote BP occurrence or be associated with DNA break repair. Using comparative genomic hybridization microarray, 57 deletions within the intron 44 to 55 region were mapped. Moreover, 21 junction fragments were sequenced to search for specific sequences. Non-randomly distributed BPs were found in introns 44, 47, 48, 49 and 53 and 50% of BPs clustered within genomic regions of less than 700bp. Repeated elements (REs), known to promote gene rearrangement via several mechanisms, were present in the vicinity of 90% of clustered BPs and less frequently (72%) close to scattered BPs, illustrating the important role of such elements in the occurrence of DMD deletions. Palindromic and TTTAAA sequences, which also promote DNA instability, were identified at fragment junctions in 20% and 5% of cases, respectively. Micro-homologies (76%) and insertions or deletions of small sequences were frequently found at BP junctions. Our results illustrate, in a large series of patients, the important role of RE and other genomic features in DNA breaks, and the involvement of different mechanisms in DMD gene deletions: Mainly replication error repair mechanisms, but also NHEJ and potentially aberrant firing of replication origins. A combination of these mechanisms may also be possible.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Univ. Littoral Côte d’Opale
Univ. Artois
Université de Lille

Collections :

• Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369

Research team(s) :

Activité Physique, Muscle, Santé (APMS)

Submission date :

2019-09-24T10:02:01Z