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The cell is constantly exposed to environmental factors damaging DNA and inhibiting DNA replication . Defense mechanism is very complex network of signaling pathways , providing coordinated DNA repair processes start and stop passing the cells through the cell cycle . This prevents damage to the amplified replication and transmission damage to daughter cells .
Currently, it is believed that DNA damage proteins are recognized by the sensor ( Rad9 , Rad1 and Hus1 ), which initiates an alarm signal transmitted to the relays, having the character type tyrosine kinases PI3 -K . These kinases (ATM , ATR ) phosphorylate effector proteins . Depending on the type of damage and the context of cellular signaling path can cause :
- Recruitment of DNA repair systems components to sites of damaged ,
- Activation of apoptosis,
- Inhibition of transcription ,
- Activation of the control system to pass through a designated cell of the cell cycle .
The first is the interface G1 / S. In most cells of DNA damage results in the phosphorylation of proteins and MDM2 Tp53 , leading to greater stability Tp53 , the tetramerization and act as a transcription factor . Among the genes whose transcription is stimulated , a gene encoding a protein p21/Waf1/Cip1 ( CDKN1 ) , cyclin-dependent kinase inhibitor , which is crucial for preventing the entry of S phase cells
If the cell at the time of injury is in the S phase , an important effector , modified by Atm is nibrin ( NBS1 ) , which is part of the complex Mre11 -Rad 50 - NBS1 acting in the repair of cracks producing double . Mutation of this protein causes despite DNA damage , DNA replication and cell progresses through S phase passes without delay. Other effectors are Brca1 and Chk2 kinase , a protein with multiple functions , frequently mutated in breast cancer.

The next control point is located in the G2 phase . The most important effector kinase Chk1 is activated by ATR or ATM -specific manner for the type of damage. Chk1 phosphorylates and inactivates the phosphatase Cdc25 . As a result, there is no p34/Cdc2 kinase activation , necessary for the cell's entry into mitosis . Simultaneously , Tp53 inhibits transcription of the genes encoding the cyclin B1 and Cdc2 , reinforcing block G2 phase .

Necessary to stop the cell checkpoint proteins are certain sensors. The following examples illustrate the interweaving of the function of certain proteins in the DNA-repair pathways and cell cycle regulation , as well as indicate that the cell has a backup retention mechanisms in the cell cycle , which is the foundation of mobile " health and safety " . Inhibitors of these mechanisms counteract damaging agents sensitize and encourage the occurrence of genetic instability , a substantial factor in the process of carcinogenesis .

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The Editorial Board
Andrzej Łukaszyk - przewodniczący, Zofia Bielańska-Osuchowska, Szczepan Biliński, Mieczysław Chorąży, Aleksander Koj, Włodzimierz Korochoda, Leszek Kuźnicki, Aleksandra Stojałowska, Lech Wojtczak

Editorial address:
Katedra i Zakład Histologii i Embriologii Uniwersytetu Medycznego w Poznaniu, ul. Święcickiego 6, 60-781 Poznań, tel. +48 61 8546453, fax. +48 61 8546440, email:

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