Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest - PubMed (original) (raw)

Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest

L C Huang et al. Proc Natl Acad Sci U S A. 1996.

Abstract

The tumor suppressor p53 contributes to maintaining genome stability by inducing a cell cycle arrest or apoptosis in response to conditions that generate DNA damage. Nuclear injection of linearized plasmid DNA, circular DNA with a large gap, or single-stranded circular phagemid is sufficient to induce a p53-dependent arrest. Supercoiled and nicked plasmid DNA, and circular DNA with a small gap were ineffective. Titration experiments indicate that the arrest mechanism in normal human fibroblasts can be activated by very few double strand breaks, and only one may be sufficient. Polymerase chain reaction assays showed that end-joining activity is low in serum-arrested human fibroblasts, and that higher joining activity occurs as cells proceed through G1 or into S phase. We propose that the exquisite sensitivity of the p53-dependent G1 arrest is partly due to inefficient repair of certain types of DNA damage in early G1.

PubMed Disclaimer

Cited by

Stress Management in Plants: Examining Provisional and Unique Dose-Dependent Responses.
Georgieva M, Vassileva V. Georgieva M, et al. Int J Mol Sci. 2023 Mar 7;24(6):5105. doi: 10.3390/ijms24065105. Int J Mol Sci. 2023. PMID: 36982199 Free PMC article. Review.
Changes in calpain-2 expression during glioblastoma progression predisposes tumor cells to temozolomide resistance by minimizing DNA damage and p53-dependent apoptosis.
Stillger MN, Chen CY, Lai ZW, Li M, Schäfer A, Pagenstecher A, Nimsky C, Bartsch JW, Schilling O. Stillger MN, et al. Cancer Cell Int. 2023 Mar 17;23(1):49. doi: 10.1186/s12935-023-02889-8. Cancer Cell Int. 2023. PMID: 36932402 Free PMC article.
Cancer and Radiosensitivity Syndromes: Is Impaired Nuclear ATM Kinase Activity the Primum Movens?
El Nachef L, Berthel E, Ferlazzo ML, Le Reun E, Al-Choboq J, Restier-Verlet J, Granzotto A, Sonzogni L, Bourguignon M, Foray N. El Nachef L, et al. Cancers (Basel). 2022 Dec 13;14(24):6141. doi: 10.3390/cancers14246141. Cancers (Basel). 2022. PMID: 36551628 Free PMC article. Review.
CRISPR Activation/Interference Screen to Identify Genetic Networks in HDAC-Inhibitor-Resistant Cells.
Jung P, Schmalbrock L, Wirth M. Jung P, et al. Methods Mol Biol. 2023;2589:429-454. doi: 10.1007/978-1-0716-2788-4_28. Methods Mol Biol. 2023. PMID: 36255641
Processing DNA lesions during mitosis to prevent genomic instability.
Audrey A, de Haan L, van Vugt MATM, de Boer HR. Audrey A, et al. Biochem Soc Trans. 2022 Aug 31;50(4):1105-1118. doi: 10.1042/BST20220049. Biochem Soc Trans. 2022. PMID: 36040211 Free PMC article. Review.

References

1. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9441-5 - PubMed
1. Cell. 1995 Oct 20;83(2):237-45 - PubMed
1. Proc Natl Acad Sci U S A. 1990 Apr;87(8):3132-6 - PubMed
1. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6166-70 - PubMed
1. Bioessays. 1990 Aug;12(8):363-9 - PubMed

Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest - PubMed (original) (raw)