RRC ID 45840
著者 Roerink SF, van Schendel R, Tijsterman M.
タイトル Polymerase theta-mediated end joining of replication-associated DNA breaks in C. elegans.
ジャーナル Genome Res
Abstract DNA lesions that block replication fork progression are drivers of cancer-associated genome alterations, but the error-prone DNA repair mechanisms acting on collapsed replication are incompletely understood, and their contribution to genome evolution largely unexplored. Here, through whole-genome sequencing of animal populations that were clonally propagated for more than 50 generations, we identify a distinct class of deletions that spontaneously accumulate in C. elegans strains lacking translesion synthesis (TLS) polymerases. Emerging DNA double-strand breaks are repaired via an error-prone mechanism in which the outermost nucleotide of one end serves to prime DNA synthesis on the other end. This pathway critically depends on the A-family polymerase theta, which protects the genome against gross chromosomal rearrangements. By comparing the genomes of isolates of C. elegans from different geographical regions, we found that in fact most spontaneously evolving structural variations match the signature of polymerase theta-mediated end joining (TMEJ), illustrating that this pathway is an important source of genetic diversification.
巻・号 24(6)
ページ 954-62
公開日 2014-6-1
DOI 10.1101/gr.170431.113
PII gr.170431.113
PMID 24614976
PMC PMC4032859
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA Breaks, Double-Stranded* DNA End-Joining Repair* DNA Polymerase theta DNA Replication DNA-Directed DNA Polymerase / genetics DNA-Directed DNA Polymerase / metabolism* Genome, Helminth Genomic Structural Variation
IF 11.093
引用数 73
WOS 分野 BIOTECHNOLOGY & APPLIED MICROBIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY GENETICS & HEREDITY
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線虫 tm2026