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A novel function for CDK2 activity at meiotic crossover sites

Palmer, Nathan ; Talib, S Zakiah A ; Singh, Priti ; Goh, Christine M F ; Liu, Kui ; Schimenti, John C and Kaldis, Philipp LU orcid (2020) In PLoS Biology 18(10).
Abstract

Genetic diversity in offspring is induced by meiotic recombination, which is initiated between homologs at >200 sites originating from meiotic double-strand breaks (DSBs). Of this initial pool, only 1-2 DSBs per homolog pair will be designated to form meiotic crossovers (COs), where reciprocal genetic exchange occurs between parental chromosomes. Cyclin-dependent kinase 2 (CDK2) is known to localize to so-called "late recombination nodules" (LRNs) marking incipient CO sites. However, the role of CDK2 kinase activity in the process of CO formation remains uncertain. Here, we describe the phenotype of 2 Cdk2 point mutants with elevated or decreased activity, respectively. Elevated CDK2 activity was associated with increased numbers of... (More)

Genetic diversity in offspring is induced by meiotic recombination, which is initiated between homologs at >200 sites originating from meiotic double-strand breaks (DSBs). Of this initial pool, only 1-2 DSBs per homolog pair will be designated to form meiotic crossovers (COs), where reciprocal genetic exchange occurs between parental chromosomes. Cyclin-dependent kinase 2 (CDK2) is known to localize to so-called "late recombination nodules" (LRNs) marking incipient CO sites. However, the role of CDK2 kinase activity in the process of CO formation remains uncertain. Here, we describe the phenotype of 2 Cdk2 point mutants with elevated or decreased activity, respectively. Elevated CDK2 activity was associated with increased numbers of LRN-associated proteins, including CDK2 itself and the MutL homolog 1 (MLH1) component of the MutLγ complex, but did not lead to increased numbers of COs. In contrast, reduced CDK2 activity leads to the complete absence of CO formation during meiotic prophase I. Our data suggest an important role for CDK2 in regulating MLH1 focus numbers and that the activity of this kinase is a key regulatory factor in the formation of meiotic COs.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS Biology
volume
18
issue
10
article number
e3000903
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:33075054
  • scopus:85094571971
ISSN
1545-7885
DOI
10.1371/journal.pbio.3000903
language
English
LU publication?
yes
id
ebd618b3-4df9-4429-a5df-a451b482a1be
date added to LUP
2020-10-26 08:35:17
date last changed
2024-05-30 23:53:33
@article{ebd618b3-4df9-4429-a5df-a451b482a1be,
  abstract     = {{<p>Genetic diversity in offspring is induced by meiotic recombination, which is initiated between homologs at &gt;200 sites originating from meiotic double-strand breaks (DSBs). Of this initial pool, only 1-2 DSBs per homolog pair will be designated to form meiotic crossovers (COs), where reciprocal genetic exchange occurs between parental chromosomes. Cyclin-dependent kinase 2 (CDK2) is known to localize to so-called "late recombination nodules" (LRNs) marking incipient CO sites. However, the role of CDK2 kinase activity in the process of CO formation remains uncertain. Here, we describe the phenotype of 2 Cdk2 point mutants with elevated or decreased activity, respectively. Elevated CDK2 activity was associated with increased numbers of LRN-associated proteins, including CDK2 itself and the MutL homolog 1 (MLH1) component of the MutLγ complex, but did not lead to increased numbers of COs. In contrast, reduced CDK2 activity leads to the complete absence of CO formation during meiotic prophase I. Our data suggest an important role for CDK2 in regulating MLH1 focus numbers and that the activity of this kinase is a key regulatory factor in the formation of meiotic COs.</p>}},
  author       = {{Palmer, Nathan and Talib, S Zakiah A and Singh, Priti and Goh, Christine M F and Liu, Kui and Schimenti, John C and Kaldis, Philipp}},
  issn         = {{1545-7885}},
  language     = {{eng}},
  number       = {{10}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS Biology}},
  title        = {{A novel function for CDK2 activity at meiotic crossover sites}},
  url          = {{http://dx.doi.org/10.1371/journal.pbio.3000903}},
  doi          = {{10.1371/journal.pbio.3000903}},
  volume       = {{18}},
  year         = {{2020}},
}