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Cell Cycle. 2006 Jun;5(12):1289-91. Epub 2006 Jun 15.

Role of mammalian Rad9 in genomic stability and ionizing radiation response.

Author information

1
Department of Radiation Oncology, Washington University School of Medicine; 4511 Forest Park Ave., St. Louis, Missouri 63108, USA. pandita@wustl.edu

Abstract

Eukaryotic cells have evolved DNA damage response mechanisms utilizing proficient DNA repair and cell cycle checkpoints in order to maintain genomic stability. The Schizosaccharomyces pombe Rad9 gene was initially identified as encoding a cell cycle checkpoint protein. When the mammalian homologue of S. pombe Rad9 was inactivated, however, chromosomal instability was observed even in the absence of DNA damaging agents. Both an increase in chromosome end-to-end associations and telomere loss were observed in cells with inactivated mammalian Rad9. This telomere instability correlated with enhanced S- and G2-phase specific cell killing, delayed kinetics of gamma-H2AX foci appearance and disappearance, and reduced chromosomal repair after ionizing radiation (IR) exposure, suggesting that Rad9 plays a role in cell cycle phase specific DNA damage repair. Inactivation of mammalian Rad9 also resulted in decreased homologous recombinational (HR) repair, which occurs predominantly in the S- and G2-phase of the cell cycle. These newly defined functions of mammalian Rad9 are discussed in relation to telomere stability and HR repair as a mechanism for promoting cell survival after IR exposure.

PMID:
16760671
DOI:
10.4161/cc.5.12.2862
[Indexed for MEDLINE]

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