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Identification PMS1 and PMS2 as potential meiotic substrates of CDK2 activity

Palmer, Nathan ; Talib, S Zakiah A ; Goh, Christine M F ; Biswas, Kajal ; Sharan, Shyam K and Kaldis, Philipp LU orcid (2023) In PLoS ONE 18(3).
Abstract

Cyclin dependent-kinase 2 (CDK2) plays important functions during the mitotic cell cycle and also facilitates several key events during germ cell development. The majority of CDK2's known meiotic functions occur during prophase of the first meiotic division. Here, CDK2 is involved in the regulation of meiotic transcription, the pairing of homologous chromosomes, and the maturation of meiotic crossover sites. Despite that some of the CDK2 substrates are known, few of them display functions in meiosis. Here, we investigate potential meiotic CDK2 substrates using in silico and in vitro approaches. We find that CDK2 phosphorylates PMS2 at Thr337, PMS1 at Thr331, and MLH1 in vitro. Phosphorylation of PMS2 affects its interaction with MLH1 to... (More)

Cyclin dependent-kinase 2 (CDK2) plays important functions during the mitotic cell cycle and also facilitates several key events during germ cell development. The majority of CDK2's known meiotic functions occur during prophase of the first meiotic division. Here, CDK2 is involved in the regulation of meiotic transcription, the pairing of homologous chromosomes, and the maturation of meiotic crossover sites. Despite that some of the CDK2 substrates are known, few of them display functions in meiosis. Here, we investigate potential meiotic CDK2 substrates using in silico and in vitro approaches. We find that CDK2 phosphorylates PMS2 at Thr337, PMS1 at Thr331, and MLH1 in vitro. Phosphorylation of PMS2 affects its interaction with MLH1 to some degree. In testis extracts from mice lacking Cdk2, there are changes in expression of PMS2, MSH2, and HEI10, which may be reflective of the loss of CDK2 phosphorylation. Our work has uncovered a few CDK2 substrates with meiotic functions, which will have to be verified in vivo. A better understanding of the CDK2 substrates will help us to gain deeper insight into the functions of this universal kinase.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Male, Mice, Animals, Phosphorylation, Mismatch Repair Endonuclease PMS2/genetics, Meiosis, Cell Cycle Checkpoints, Cyclin-Dependent Kinase 2/genetics, Prophase
in
PLoS ONE
volume
18
issue
3
article number
e0283590
pages
19 pages
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:36952545
  • scopus:85150711212
ISSN
1932-6203
DOI
10.1371/journal.pone.0283590
language
English
LU publication?
yes
id
2991ea55-570c-4229-bbb4-5392d8d2830e
date added to LUP
2023-03-28 09:40:05
date last changed
2024-06-15 01:43:09
@article{2991ea55-570c-4229-bbb4-5392d8d2830e,
  abstract     = {{<p>Cyclin dependent-kinase 2 (CDK2) plays important functions during the mitotic cell cycle and also facilitates several key events during germ cell development. The majority of CDK2's known meiotic functions occur during prophase of the first meiotic division. Here, CDK2 is involved in the regulation of meiotic transcription, the pairing of homologous chromosomes, and the maturation of meiotic crossover sites. Despite that some of the CDK2 substrates are known, few of them display functions in meiosis. Here, we investigate potential meiotic CDK2 substrates using in silico and in vitro approaches. We find that CDK2 phosphorylates PMS2 at Thr337, PMS1 at Thr331, and MLH1 in vitro. Phosphorylation of PMS2 affects its interaction with MLH1 to some degree. In testis extracts from mice lacking Cdk2, there are changes in expression of PMS2, MSH2, and HEI10, which may be reflective of the loss of CDK2 phosphorylation. Our work has uncovered a few CDK2 substrates with meiotic functions, which will have to be verified in vivo. A better understanding of the CDK2 substrates will help us to gain deeper insight into the functions of this universal kinase.</p>}},
  author       = {{Palmer, Nathan and Talib, S Zakiah A and Goh, Christine M F and Biswas, Kajal and Sharan, Shyam K and Kaldis, Philipp}},
  issn         = {{1932-6203}},
  keywords     = {{Male; Mice; Animals; Phosphorylation; Mismatch Repair Endonuclease PMS2/genetics; Meiosis; Cell Cycle Checkpoints; Cyclin-Dependent Kinase 2/genetics; Prophase}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{3}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Identification PMS1 and PMS2 as potential meiotic substrates of CDK2 activity}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0283590}},
  doi          = {{10.1371/journal.pone.0283590}},
  volume       = {{18}},
  year         = {{2023}},
}