The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ

Kouji Hirota, Kazunori Yoshikiyo, Guillaume Guilbaud, Toshiki Tsurimoto, Junko Murai, Masataka Tsuda, Lara G. Phillips, Takeo Narita, Kana Nishihara, Kaori Kobayashi, Kouich Yamada, Jun Nakamura, Yves Pommier, Alan Lehmann, Julian E. Sale, Shunichi Takeda

研究成果: ジャーナルへの寄稿記事

23 引用 (Scopus)

抄録

The replicative DNA polymerase Polδ consists of a catalytic subunit POLD1/p125 and three regulatory subunits POLD2/p50, POLD3/p66 and POLD4/p12. The ortholog of POLD3 in Saccharomyces cerevisiae, Pol32, is required for a significant proportion of spontaneous and UV-induced mutagenesis through its additional role in translesion synthesis (TLS) as a subunit of DNA polymerase ζ. Remarkably, chicken DT40 B lymphocytes deficient in POLD3 are viable and able to replicate undamaged genomic DNA with normal kinetics. Like its counterpart in yeast, POLD3 is required for fully effective TLS, its loss resulting in hypersensitivity to a variety of DNA damaging agents, a diminished ability to maintain replication fork progression after UV irradiation and a significant decrease in abasic site-induced mutagenesis in the immunoglobulin loci. However, these defects appear to be largely independent of Polζ, suggesting that POLD3 makes a significant contribution to TLS independently of Polζ in DT40 cells. Indeed, combining polη, polζ and pold3 mutations results in synthetic lethality. Additionally, we show in vitro that POLD3 promotes extension beyond an abasic by the Polδ holoenzyme suggesting that while POLD3 is not required for normal replication, it may help Polδ to complete abasic site bypass independently of canonical TLS polymerases.

元の言語英語
ページ(範囲)1671-1683
ページ数13
ジャーナルNucleic acids research
43
発行部数3
DOI
出版物ステータス出版済み - 1 1 2015

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DNA-Directed DNA Polymerase
Mutagenesis
Holoenzymes
DNA
Saccharomyces cerevisiae
Immunoglobulins
Chickens
Catalytic Domain
Hypersensitivity
B-Lymphocytes
Yeasts
Mutation
Synthetic Lethal Mutations
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Genetics

これを引用

The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ. / Hirota, Kouji; Yoshikiyo, Kazunori; Guilbaud, Guillaume; Tsurimoto, Toshiki; Murai, Junko; Tsuda, Masataka; Phillips, Lara G.; Narita, Takeo; Nishihara, Kana; Kobayashi, Kaori; Yamada, Kouich; Nakamura, Jun; Pommier, Yves; Lehmann, Alan; Sale, Julian E.; Takeda, Shunichi.

:: Nucleic acids research, 巻 43, 番号 3, 01.01.2015, p. 1671-1683.

研究成果: ジャーナルへの寄稿記事

Hirota, K, Yoshikiyo, K, Guilbaud, G, Tsurimoto, T, Murai, J, Tsuda, M, Phillips, LG, Narita, T, Nishihara, K, Kobayashi, K, Yamada, K, Nakamura, J, Pommier, Y, Lehmann, A, Sale, JE & Takeda, S 2015, 'The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ', Nucleic acids research, 巻. 43, 番号 3, pp. 1671-1683. https://doi.org/10.1093/nar/gkv023
Hirota, Kouji ; Yoshikiyo, Kazunori ; Guilbaud, Guillaume ; Tsurimoto, Toshiki ; Murai, Junko ; Tsuda, Masataka ; Phillips, Lara G. ; Narita, Takeo ; Nishihara, Kana ; Kobayashi, Kaori ; Yamada, Kouich ; Nakamura, Jun ; Pommier, Yves ; Lehmann, Alan ; Sale, Julian E. ; Takeda, Shunichi. / The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ. :: Nucleic acids research. 2015 ; 巻 43, 番号 3. pp. 1671-1683.
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abstract = "The replicative DNA polymerase Polδ consists of a catalytic subunit POLD1/p125 and three regulatory subunits POLD2/p50, POLD3/p66 and POLD4/p12. The ortholog of POLD3 in Saccharomyces cerevisiae, Pol32, is required for a significant proportion of spontaneous and UV-induced mutagenesis through its additional role in translesion synthesis (TLS) as a subunit of DNA polymerase ζ. Remarkably, chicken DT40 B lymphocytes deficient in POLD3 are viable and able to replicate undamaged genomic DNA with normal kinetics. Like its counterpart in yeast, POLD3 is required for fully effective TLS, its loss resulting in hypersensitivity to a variety of DNA damaging agents, a diminished ability to maintain replication fork progression after UV irradiation and a significant decrease in abasic site-induced mutagenesis in the immunoglobulin loci. However, these defects appear to be largely independent of Polζ, suggesting that POLD3 makes a significant contribution to TLS independently of Polζ in DT40 cells. Indeed, combining polη, polζ and pold3 mutations results in synthetic lethality. Additionally, we show in vitro that POLD3 promotes extension beyond an abasic by the Polδ holoenzyme suggesting that while POLD3 is not required for normal replication, it may help Polδ to complete abasic site bypass independently of canonical TLS polymerases.",
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T1 - The POLD3 subunit of DNA polymerase δ can promote translesion synthesis independently of DNA polymerase ζ

AU - Hirota, Kouji

AU - Yoshikiyo, Kazunori

AU - Guilbaud, Guillaume

AU - Tsurimoto, Toshiki

AU - Murai, Junko

AU - Tsuda, Masataka

AU - Phillips, Lara G.

AU - Narita, Takeo

AU - Nishihara, Kana

AU - Kobayashi, Kaori

AU - Yamada, Kouich

AU - Nakamura, Jun

AU - Pommier, Yves

AU - Lehmann, Alan

AU - Sale, Julian E.

AU - Takeda, Shunichi

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