A distinct circular DNA profile intersects with proteome changes in the genotoxic stress-related hSOD1^G93A model of ALS.

ABSTRACT:

Background

Numerous genes, including SOD1, mutated in familial and sporadic amyotrophic lateral sclerosis (f/sALS) share a role in DNA damage and repair, emphasizing genome disintegration in ALS. One possible outcome of chromosomal instability and repair processes is extrachromosomal circular DNA (eccDNA) formation. Therefore, eccDNA might accumulate in f/sALS with yet unknown function.

Methods

We combined rolling circle amplification with linear DNA digestion to purify eccDNA from the cervical spinal cord of 9 co-isogenic symptomatic hSOD1^G93A mutants and 10 controls, followed by deep short-read sequencing. We mapped the eccDNAs and performed differential analysis based on the split read signal of the eccDNAs, referred as DifCir, between the ALS and control speci

SUBMITTER: Gerovska D 

PROVIDER: S-EPMC10498603 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature