Cell cycle phase dependent role of DNA polymerase beta in DNA repair and survival after ionizing radiation.
OBJECTIVE
The purpose of the present study was to determine the role of DNA polymerase beta in repair and response after ionizing radiation in different phases of the cell cycle.


METHODS
Synchronized cells deficient and proficient in DNA polymerase beta were irradiated in different phases of the cell cycle as determined by BrdU/flow cytometry. Cell kill and DNA repair were assessed by colony formation and alkaline comet assays, respectively.


RESULTS
We first demonstrated delayed repair of ionizing radiation induced DNA damage in confluent polymerase beta deficient cells. Cell synchronization experiments revealed a cell cycle phase dependence by demonstrating radiation hypersensitivity of polymerase beta-deficient cells in G1, but not in the S-phase. Complementing polymerase beta-deficient cells with polymerase beta reverted the hypersensitivity in G1. Ionizing radiation damage repair was found to be delayed in beta-deficient cells when irradiated in G1, but not in S.


CONCLUSIONS
The data show a differential role of DNA polymerase beta driven base excision and single strand break repair throughout the cell cycle after ionizing radiation damage.
Vermeulen
Christie
C
Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Verwijs-Janssen
Manon
M
Begg
Adrian C
AC
Vens
Conchita
C
D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects*; D002460:Cell Line; D053904:DNA Breaks, Single-Stranded / Q000528:radiation effects*; D019951:DNA Polymerase beta / Q000378:metabolism*; D004260:DNA Repair / Q000528:radiation effects*; D051379:Mice; D011833:Radiation Injuries, Experimental; D011836:Radiation Tolerance; D011839:Radiation, Ionizing
D019951:DNA Polymerase beta