MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis.
Two eukaryotic pathways for processing double-strand breaks (DSBs) as crossovers have been described, one dependent on the MutL homologs Mlh1 and Mlh3, and the other on the structure-specific endonuclease Mus81. Mammalian MUS81 has been implicated in maintenance of genomic stability in somatic cells...
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2008-09-01
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doaj-f7e35bdf899f4956aaa54dc07f58ff8d2020-11-25T01:52:52ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042008-09-0149e100018610.1371/journal.pgen.1000186MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis.J Kim HollowayJames BoothWinfried EdelmannClare H McGowanPaula E CohenTwo eukaryotic pathways for processing double-strand breaks (DSBs) as crossovers have been described, one dependent on the MutL homologs Mlh1 and Mlh3, and the other on the structure-specific endonuclease Mus81. Mammalian MUS81 has been implicated in maintenance of genomic stability in somatic cells; however, little is known about its role during meiosis. Mus81-deficient mice were originally reported as being viable and fertile, with normal meiotic progression; however, a more detailed examination of meiotic progression in Mus81-null animals and WT controls reveals significant meiotic defects in the mutants. These include smaller testis size, a depletion of mature epididymal sperm, significantly upregulated accumulation of MLH1 on chromosomes from pachytene meiocytes in an interference-independent fashion, and a subset of meiotic DSBs that fail to be repaired. Interestingly, chiasmata numbers in spermatocytes from Mus81-/- animals are normal, suggesting additional integrated mechanisms controlling the two distinct crossover pathways. This study is the first in-depth analysis of meiotic progression in Mus81-nullizygous mice, and our results implicate the MUS81 pathway as a regulator of crossover frequency and placement in mammals.http://europepmc.org/articles/PMC2525838?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
J Kim Holloway James Booth Winfried Edelmann Clare H McGowan Paula E Cohen |
spellingShingle |
J Kim Holloway James Booth Winfried Edelmann Clare H McGowan Paula E Cohen MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis. PLoS Genetics |
author_facet |
J Kim Holloway James Booth Winfried Edelmann Clare H McGowan Paula E Cohen |
author_sort |
J Kim Holloway |
title |
MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis. |
title_short |
MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis. |
title_full |
MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis. |
title_fullStr |
MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis. |
title_full_unstemmed |
MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis. |
title_sort |
mus81 generates a subset of mlh1-mlh3-independent crossovers in mammalian meiosis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Genetics |
issn |
1553-7390 1553-7404 |
publishDate |
2008-09-01 |
description |
Two eukaryotic pathways for processing double-strand breaks (DSBs) as crossovers have been described, one dependent on the MutL homologs Mlh1 and Mlh3, and the other on the structure-specific endonuclease Mus81. Mammalian MUS81 has been implicated in maintenance of genomic stability in somatic cells; however, little is known about its role during meiosis. Mus81-deficient mice were originally reported as being viable and fertile, with normal meiotic progression; however, a more detailed examination of meiotic progression in Mus81-null animals and WT controls reveals significant meiotic defects in the mutants. These include smaller testis size, a depletion of mature epididymal sperm, significantly upregulated accumulation of MLH1 on chromosomes from pachytene meiocytes in an interference-independent fashion, and a subset of meiotic DSBs that fail to be repaired. Interestingly, chiasmata numbers in spermatocytes from Mus81-/- animals are normal, suggesting additional integrated mechanisms controlling the two distinct crossover pathways. This study is the first in-depth analysis of meiotic progression in Mus81-nullizygous mice, and our results implicate the MUS81 pathway as a regulator of crossover frequency and placement in mammals. |
url |
http://europepmc.org/articles/PMC2525838?pdf=render |
work_keys_str_mv |
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