Complex correlations: replication timing and mutational landscapes during cancer and genome evolution.
Curr Opin Genet Dev
; 25: 93-100, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24598232
ABSTRACT
A recent flurry of reports correlates replication timing (RT) with mutation rates during both evolution and cancer. Specifically, point mutations and copy number losses correlate with late replication, while copy number gains and other rearrangements correlate with early replication. In some cases, plausible mechanisms have been proposed. Point mutation rates may reflect temporal variation in repair mechanisms. Transcription-induced double-strand breaks are expected to occur in transcriptionally active early replicating chromatin. Fusion partners are generally in close proximity, and chromatin in close proximity replicates at similar times. However, temporal enrichment of copy number gains and losses remains an enigma. Moreover, many conclusions are compromised by a lack of matched RT and sequence datasets, the filtering out of developmental variation in RT, and the use of somatic cell lines to make inferences about germline evolution.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Genoma Humano
/
Replicação do DNA
/
Mutação
/
Neoplasias
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article