Homologous chromosomes make contact at the sites of double-strand breaks in genes in somatic G0/G1-phase human cells.
Proc Natl Acad Sci U S A
; 109(24): 9454-9, 2012 Jun 12.
Article
en En
| MEDLINE
| ID: mdl-22645362
ABSTRACT
Double-strand DNA breaks (DSBs) are continuously induced in cells by endogenously generated free radicals and exogenous genotoxic agents such as ionizing radiation. DSBs activate the kinase activity in sensor proteins such as ATM and DNA-PK, initiating a complex DNA damage response that coordinates various DNA repair pathways to restore genomic integrity. In this study, we report the unexpected finding that homologous chromosomes contact each other at the sites of DSBs induced by either radiation or the endonuclease I-PpoI in human somatic cells. Contact involves short segments of homologous chromosomes and is centered on a DSB in active genes but does not occur at I-PpoI sites in intergenic DNA. I-PpoI-induced contact between homologous genes is abrogated by the transcriptional inhibitors actinomycin D and α-amanitin and requires the kinase activity of ATM but not DNA-PK. Our findings provide documentation of a common transcription-related and ATM kinase-dependent mechanism that induces contact between allelic regions of homologous chromosomes at sites of DSBs in human somatic cells.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Fase de Descanso del Ciclo Celular
/
Fase G1
/
Cromosomas Humanos
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos