Mitosis, double strand break repair, and telomeres: a view from the end: how telomeres and the DNA damage response cooperate during mitosis to maintain genome stability.
Bioessays
; 36(11): 1054-61, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-25171524
ABSTRACT
Double strand break (DSB) repair is suppressed during mitosis because RNF8 and downstream DNA damage response (DDR) factors, including 53BP1, do not localize to mitotic chromatin. Discovery of the mitotic kinase-dependent mechanism that inhibits DSB repair during cell division was recently reported. It was shown that restoring mitotic DSB repair was detrimental, resulting in repair dependent genome instability and covalent telomere fusions. The telomere DDR that occurs naturally during cellular aging and in cancer is known to be refractory to G2/M checkpoint activation. Such DDR-positive telomeres, and those that occur as part of the telomere-dependent prolonged mitotic arrest checkpoint, normally pass through mitosis without covalent ligation, but result in cell growth arrest in G1 phase. The discovery that suppressing DSB repair during mitosis may function primarily to protect DDR-positive telomeres from fusing during cell division reinforces the unique cooperation between telomeres and the DDR to mediate tumor suppression.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Telômero
/
Instabilidade Genômica
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Reparo do DNA
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Quebras de DNA de Cadeia Dupla
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Mitose
Limite:
Humans
Idioma:
En
Revista:
Bioessays
Assunto da revista:
BIOLOGIA
/
BIOLOGIA MOLECULAR
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Austrália