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

Content Provider	PubMed Central
Author	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
Copyright Year	2015
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.
Related Links	http://dx.doi.org/10.1093/nar/gkv023
Ending Page	1683
Page Count	13
Starting Page	1671
File Format	PDF
ISSN	03051048
e-ISSN	13624962
Journal	Nucleic Acids Research
Issue Number	3
Volume Number	43
Language	English
Publisher	Oxford University Press
Publisher Date	2015-02-18
Access Restriction	Open
Rights Holder	Oxford University Press
Subject Keyword	Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics

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