TY - JOUR
T1 - Vertebrate POLQ and POLβ Cooperate in Base Excision Repair of Oxidative DNA Damage
AU - Yoshimura, Michio
AU - Kohzaki, Masaoki
AU - Nakamura, Jun
AU - Asagoshi, Kenjiro
AU - Sonoda, Eiichiro
AU - Hou, Esther
AU - Prasad, Rajendra
AU - Wilson, Samuel H.
AU - Tano, Keizo
AU - Yasui, Akira
AU - Lan, Li
AU - Seki, Mineaki
AU - Wood, Richard D.
AU - Arakawa, Hiroshi
AU - Buerstedde, Jean Marie
AU - Hochegger, Helfrid
AU - Okada, Takashi
AU - Hiraoka, Masahiro
AU - Takeda, Shunichi
N1 - Funding Information:
We would like to thank H. Onisawa, Y. Murakawa, A. Ohno, and S. Torikoshi for their technical assistance. We also acknowledge Drs. A. Lehmann, K. Caldecott, and C. Breslin for critical reading and suggestion. Financial support was provided in part by grant of Core Research for Evolutional Science and Technology (CREST) from Japan Science and Technology Corporation, by the Center of Excellence (COE) grant for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of the Japanese government, by grants from The Uehara Memorial Foundation and The Naito Foundation, by NIEHS grant P30-ES10126 to J.N., and by NIH grant CA101980 to R.D.W. This research was also supported in part by the Intramural Research Program of the NIH.
PY - 2006/10/6
Y1 - 2006/10/6
N2 - Base excision repair (BER) plays an essential role in protecting cells from mutagenic base damage caused by oxidative stress, hydrolysis, and environmental factors. POLQ is a DNA polymerase, which appears to be involved in translesion DNA synthesis (TLS) past base damage. We disrupted POLQ, and its homologs HEL308 and POLN in chicken DT40 cells, and also created polq/hel308 and polq/poln double mutants. We found that POLQ-deficient mutants exhibit hypersensitivity to oxidative base damage induced by H2O2, but not to UV or cisplatin. Surprisingly, this phenotype was synergistically increased by concomitant deletion of the major BER polymerase, POLβ. Moreover, extracts from a polq null mutant cell line show reduced BER activity, and POLQ, like POLβ, accumulated rapidly at sites of base damage. Accordingly, POLQ and POLβ share an overlapping function in the repair of oxidative base damage. Taken together, these results suggest a role for vertebrate POLQ in BER.
AB - Base excision repair (BER) plays an essential role in protecting cells from mutagenic base damage caused by oxidative stress, hydrolysis, and environmental factors. POLQ is a DNA polymerase, which appears to be involved in translesion DNA synthesis (TLS) past base damage. We disrupted POLQ, and its homologs HEL308 and POLN in chicken DT40 cells, and also created polq/hel308 and polq/poln double mutants. We found that POLQ-deficient mutants exhibit hypersensitivity to oxidative base damage induced by H2O2, but not to UV or cisplatin. Surprisingly, this phenotype was synergistically increased by concomitant deletion of the major BER polymerase, POLβ. Moreover, extracts from a polq null mutant cell line show reduced BER activity, and POLQ, like POLβ, accumulated rapidly at sites of base damage. Accordingly, POLQ and POLβ share an overlapping function in the repair of oxidative base damage. Taken together, these results suggest a role for vertebrate POLQ in BER.
KW - DNA
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U2 - 10.1016/j.molcel.2006.07.032
DO - 10.1016/j.molcel.2006.07.032
M3 - Article
C2 - 17018297
AN - SCOPUS:33749315817
SN - 1097-2765
VL - 24
SP - 115
EP - 125
JO - Molecular cell
JF - Molecular cell
IS - 1
ER -