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Disruption of mouse polymerase ζ (Rev3) leads to embryonic lethality and impairs blastocyst development in vitro

Bemark, Mats LU orcid ; Khamlichi, Amine A. ; Davies, Sarah L. and Neuberger, Michael S. (2000) In Current Biology 10(19). p.1213-1216
Abstract

Multiple DNA polymerases exist in eukaryotes. Polymerases α, δ and ε are mainly responsible for chromosomal DNA replication in the nucleus and are required for proliferation. In contrast, the repair polymerases β and η are not essential for cellular proliferation in yeast or mice, but a lack of either polymerase can lead, respectively, to defects in base excision repair or the ability to replicate past lesions induced by ultraviolet (UV) radiation [1-3]. Here, we have focused on polymerase ζ. This was first described as a non-essential product of the yeast REV3/REV7 genes involved in UV-induced mutagenesis, and was later implicated in trans-lesion synthesis [4,5]. Unlike in yeast, the mouse homologue (mRev3) was found to be essential... (More)

Multiple DNA polymerases exist in eukaryotes. Polymerases α, δ and ε are mainly responsible for chromosomal DNA replication in the nucleus and are required for proliferation. In contrast, the repair polymerases β and η are not essential for cellular proliferation in yeast or mice, but a lack of either polymerase can lead, respectively, to defects in base excision repair or the ability to replicate past lesions induced by ultraviolet (UV) radiation [1-3]. Here, we have focused on polymerase ζ. This was first described as a non-essential product of the yeast REV3/REV7 genes involved in UV-induced mutagenesis, and was later implicated in trans-lesion synthesis [4,5]. Unlike in yeast, the mouse homologue (mRev3) was found to be essential for life. Homozygous mutant mice died in utero. Mutant embryos were considerably reduced in size at day 10.5 of development and usually aborted around day 12.5. It is likely that this block reflects a need for mRev3 in proliferative clonal expansion (rather than in the production of a particular cell type) as mutant blastocysts showed greatly diminished expansion of the inner cell mass in culture. Titus, mRev3 could be required to repair a form of externally induced DNA damage that otherwise accumulates during clonal expansion or, consistent with the high homology shared between its Rev7 partner and the mitotic checkpoint gene product Mad2 [6], mRev3 might play a role in cell proliferation and genomic stability even in the absence of environmentally induced damage.

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author
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publishing date
type
Contribution to journal
publication status
published
subject
in
Current Biology
volume
10
issue
19
pages
1213 - 1216
publisher
Elsevier
external identifiers
  • scopus:0034609744
  • pmid:11050391
ISSN
0960-9822
DOI
10.1016/S0960-9822(00)00724-7
language
English
LU publication?
no
additional info
Funding Information: We thank Gareth Williams for assistance in the cloning of mRev3 , Julian Sale, K.J. Patel and Azim Surani for advice and Martin Johnson for very helpful suggestions. M.B. was supported by a grant from the Swedish Cancer Society and A.A.K. by grants from HFSPO and PDZR-Limousin.
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feaa0504-c659-486a-ad66-de68e66473df
date added to LUP
2023-12-06 17:12:44
date last changed
2025-06-01 02:13:24
@article{feaa0504-c659-486a-ad66-de68e66473df,
  abstract     = {{<p>Multiple DNA polymerases exist in eukaryotes. Polymerases α, δ and ε are mainly responsible for chromosomal DNA replication in the nucleus and are required for proliferation. In contrast, the repair polymerases β and η are not essential for cellular proliferation in yeast or mice, but a lack of either polymerase can lead, respectively, to defects in base excision repair or the ability to replicate past lesions induced by ultraviolet (UV) radiation [1-3]. Here, we have focused on polymerase ζ. This was first described as a non-essential product of the yeast REV3/REV7 genes involved in UV-induced mutagenesis, and was later implicated in trans-lesion synthesis [4,5]. Unlike in yeast, the mouse homologue (mRev3) was found to be essential for life. Homozygous mutant mice died in utero. Mutant embryos were considerably reduced in size at day 10.5 of development and usually aborted around day 12.5. It is likely that this block reflects a need for mRev3 in proliferative clonal expansion (rather than in the production of a particular cell type) as mutant blastocysts showed greatly diminished expansion of the inner cell mass in culture. Titus, mRev3 could be required to repair a form of externally induced DNA damage that otherwise accumulates during clonal expansion or, consistent with the high homology shared between its Rev7 partner and the mitotic checkpoint gene product Mad2 [6], mRev3 might play a role in cell proliferation and genomic stability even in the absence of environmentally induced damage.</p>}},
  author       = {{Bemark, Mats and Khamlichi, Amine A. and Davies, Sarah L. and Neuberger, Michael S.}},
  issn         = {{0960-9822}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{19}},
  pages        = {{1213--1216}},
  publisher    = {{Elsevier}},
  series       = {{Current Biology}},
  title        = {{Disruption of mouse polymerase ζ (Rev3) leads to embryonic lethality and impairs blastocyst development in vitro}},
  url          = {{http://dx.doi.org/10.1016/S0960-9822(00)00724-7}},
  doi          = {{10.1016/S0960-9822(00)00724-7}},
  volume       = {{10}},
  year         = {{2000}},
}