Mammalian Rad9 plays a role in telomere stability, S- and G 2-phase-specific cell survival, and homologous recombinational repair

Raj K. Pandita, Girdhar G. Sharma, Andrei Laszlo, Kevin M. Hopkins, Scott Davey, Mikhail Chakhparonian, Arun Gupta, Raymund J. Wellinger, Junran Zhang, Simon N. Powell, Joseph L. Roti Roti, Howard B. Lieberman, Tej K. Pandita

Research output: Contribution to journalArticle

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Abstract

The protein products of several rad checkpoint genes of Schizosaccharomyces pombe (rad1+, rad3+, rad9+, rad17+, rad26+, and hus1+) play crucial roles in sensing changes in DNA structure, and several function in the maintenance of telomeres. When the mammalian homologue of S. pombe Rad9 was inactivated, increases in chromosome end-to-end associations and frequency of telomere loss were observed. This telomere instability correlated with enhanced S- and G2-phase- specific cell killing, delayed kinetics of γ-H2AX focus 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. Furthermore, mammalian Rad9 interacted with Rad51, and inactivation of mammalian Rad9 also resulted in decreased homologous recombinational (HR) repair, which occurs predominantly in the S and G 2 phases of the cell cycle. Together, these findings provide evidence of roles for mammalian Rad9 in telomere stability and HR repair as a mechanism for promoting cell survival after IR exposure.

Original languageEnglish (US)
Pages (from-to)1850-1864
Number of pages15
JournalMolecular and Cellular Biology
Volume26
Issue number5
DOIs
StatePublished - Mar 2006

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Recombinational DNA Repair
Telomere
Cell Survival
Schizosaccharomyces
Ionizing Radiation
Cell Cycle
G2 Phase
S Phase
DNA Repair
DNA Damage
Chromosomes
Maintenance
DNA
Genes
Proteins
Radiation Exposure

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Pandita, R. K., Sharma, G. G., Laszlo, A., Hopkins, K. M., Davey, S., Chakhparonian, M., ... Pandita, T. K. (2006). Mammalian Rad9 plays a role in telomere stability, S- and G 2-phase-specific cell survival, and homologous recombinational repair. Molecular and Cellular Biology, 26(5), 1850-1864. https://doi.org/10.1128/MCB.26.5.1850-1864.2006

Mammalian Rad9 plays a role in telomere stability, S- and G 2-phase-specific cell survival, and homologous recombinational repair. / Pandita, Raj K.; Sharma, Girdhar G.; Laszlo, Andrei; Hopkins, Kevin M.; Davey, Scott; Chakhparonian, Mikhail; Gupta, Arun; Wellinger, Raymund J.; Zhang, Junran; Powell, Simon N.; Roti Roti, Joseph L.; Lieberman, Howard B.; Pandita, Tej K.

In: Molecular and Cellular Biology, Vol. 26, No. 5, 03.2006, p. 1850-1864.

Research output: Contribution to journalArticle

Pandita, RK, Sharma, GG, Laszlo, A, Hopkins, KM, Davey, S, Chakhparonian, M, Gupta, A, Wellinger, RJ, Zhang, J, Powell, SN, Roti Roti, JL, Lieberman, HB & Pandita, TK 2006, 'Mammalian Rad9 plays a role in telomere stability, S- and G 2-phase-specific cell survival, and homologous recombinational repair', Molecular and Cellular Biology, vol. 26, no. 5, pp. 1850-1864. https://doi.org/10.1128/MCB.26.5.1850-1864.2006
Pandita, Raj K. ; Sharma, Girdhar G. ; Laszlo, Andrei ; Hopkins, Kevin M. ; Davey, Scott ; Chakhparonian, Mikhail ; Gupta, Arun ; Wellinger, Raymund J. ; Zhang, Junran ; Powell, Simon N. ; Roti Roti, Joseph L. ; Lieberman, Howard B. ; Pandita, Tej K. / Mammalian Rad9 plays a role in telomere stability, S- and G 2-phase-specific cell survival, and homologous recombinational repair. In: Molecular and Cellular Biology. 2006 ; Vol. 26, No. 5. pp. 1850-1864.
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