p21 inhibits Cdk1 in the absence of Cdk2 to maintain the G1/S phase DNA damage checkpoint
Satyanarayana, Ande ; Hilton, Mary Beth and Kaldis, Philipp LU
(2008)
In Molecular Biology of the Cell
19(1).
p.65-77
- Abstract
Cdk1 was proposed to compensate for the loss of Cdk2. Here we present evidence that this is possible due to premature translocation of Cdk1 from the cytoplasm to the nucleus in the absence of Cdk2. We also investigated the consequence of loss of Cdk2 on the maintenance of the G1/S DNA damage checkpoint. Cdk2-/- mouse embryonic fibroblasts in vitro as well as regenerating liver cells after partial hepatectomy (PH) in Cdk2-/- mice, arrest promptly at the G1/S checkpoint in response to γ-irradiation due to activation of p53 and p21 inhibiting Cdk1. Furthermore re-entry into S phase after irradiation was delayed in Cdk2-/- cells due to prolonged and impaired DNA repair activity. In addition,... (More)
Cdk1 was proposed to compensate for the loss of Cdk2. Here we present evidence that this is possible due to premature translocation of Cdk1 from the cytoplasm to the nucleus in the absence of Cdk2. We also investigated the consequence of loss of Cdk2 on the maintenance of the G1/S DNA damage checkpoint. Cdk2-/- mouse embryonic fibroblasts in vitro as well as regenerating liver cells after partial hepatectomy (PH) in Cdk2-/- mice, arrest promptly at the G1/S checkpoint in response to γ-irradiation due to activation of p53 and p21 inhibiting Cdk1. Furthermore re-entry into S phase after irradiation was delayed in Cdk2-/- cells due to prolonged and impaired DNA repair activity. In addition, Cdk2-/- mice were more sensitive to lethal irradiation compared to wild-type and displayed delayed resumption of DNA replication in regenerating liver cells. Our results suggest that the G1/S DNA damage checkpoint is intact in the absence of Cdk2, but Cdk2 is important for proper repair of the damaged DNA.
(Less)
- author
- Satyanarayana, Ande
; Hilton, Mary Beth
and Kaldis, Philipp
LU
- publishing date
- 2008-01-01
- type
- Contribution to journal
- publication status
- published
- in
- Molecular Biology of the Cell
- volume
- 19
- issue
- 1
- pages
- 65 - 77
- publisher
- American Society for Cell Biology
- external identifiers
-
- pmid:17942597
- scopus:38749103066
- ISSN
- 1059-1524
- DOI
- 10.1091/mbc.E07-06-0525
- language
- English
- LU publication?
- no
- id
- 4a812910-c684-4c6c-9bce-5209a04dfe66
- date added to LUP
- 2019-09-18 14:14:22
- date last changed
- 2024-08-08 07:04:37
@article{4a812910-c684-4c6c-9bce-5209a04dfe66,
abstract = {{<p>Cdk1 was proposed to compensate for the loss of Cdk2. Here we present evidence that this is possible due to premature translocation of Cdk1 from the cytoplasm to the nucleus in the absence of Cdk2. We also investigated the consequence of loss of Cdk2 on the maintenance of the G1/S DNA damage checkpoint. Cdk2<sup>-/-</sup> mouse embryonic fibroblasts in vitro as well as regenerating liver cells after partial hepatectomy (PH) in Cdk2<sup>-/-</sup> mice, arrest promptly at the G1/S checkpoint in response to γ-irradiation due to activation of p53 and p21 inhibiting Cdk1. Furthermore re-entry into S phase after irradiation was delayed in Cdk2<sup>-/-</sup> cells due to prolonged and impaired DNA repair activity. In addition, Cdk2<sup>-/-</sup> mice were more sensitive to lethal irradiation compared to wild-type and displayed delayed resumption of DNA replication in regenerating liver cells. Our results suggest that the G1/S DNA damage checkpoint is intact in the absence of Cdk2, but Cdk2 is important for proper repair of the damaged DNA.</p>}},
author = {{Satyanarayana, Ande and Hilton, Mary Beth and Kaldis, Philipp}},
issn = {{1059-1524}},
language = {{eng}},
month = {{01}},
number = {{1}},
pages = {{65--77}},
publisher = {{American Society for Cell Biology}},
series = {{Molecular Biology of the Cell}},
title = {{p21 inhibits Cdk1 in the absence of Cdk2 to maintain the G1/S phase DNA damage checkpoint}},
url = {{http://dx.doi.org/10.1091/mbc.E07-06-0525}},
doi = {{10.1091/mbc.E07-06-0525}},
volume = {{19}},
year = {{2008}},
}