Concerted control of DNA double strand break repair and cell cycle progression in X-irradiated mammalian cells

• Autorzy: Sochanowicz B. , Szumiel I.
• Języki publikacji: EN

Abstrakty

EN

Upon examination of cell cycle regulation in a damaged cell, relations were discovered of the cell cycle control mechanisms with a complicated web of signalling pathways, eventually called the genome surveillance system. After infliction of DNA double strand breaks (DSB), the signalling is initiated by sensor proteins and transducer protein kinase ATM. This kinase phosphorylates downstream effector proteins, such as checkpoint kinases CHK1 and CHK2, which initiate the pathways leading to cell cycle arrest. In contrast with the older model of linear transmission of signals in a certain sequence, it is now accepted that the damage signalling system is branched and contains feedback loops. DSB's presence is signalled by sensor proteins (MRE11-RAD50-nibrin complex, MRN) to ATM and the signal is amplified through adaptor proteins, MDC1/NFBD1 or 53BP1 (Tp53 binding protein). MRN contains a forkheadassociated (FHA) domain and BRCA1 carboxyl-terminal (BRCT) domain. The combination of the FHA/BRCT domains has a crucial role for the binding of nibrin to the H2AX histone, assembling the components of repair foci. These domains also are important for interaction of other proteins localised in the foci. For example, MDC1/NFBD1 contains a FHA domain and two BRCT domains which are involved in protein interactions. The signal generated at DSBs is amplified and transduced to recruit components of DNA repair systems. In a concerted way with the sequential recruitment of components of repair foci, activation of transcription of genes takes place, that is necessary for blocking progression through the cell cycle, for DNA repair or apoptosis.

Słowa kluczowe

EN

ATM kinase; DNA double strand break repair; RAD50; cell cycle arrest; repair foci; BRCT domain

• Wydawca: Institute of Nuclear Chemistry and Technology
• Czasopismo: Nukleonika
• Rocznik: 2005
• Tom: Vol. 50, nr 4
• Strony: 129--138
• Opis fizyczny: Bibliogr. 58 poz., rys.

Twórcy

autor

Sochanowicz B.

• Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, 16 Dorodna Str., 03-195 Warsaw, Poland, Tel.: [phone], Fax: [phone]

autor

Szumiel I.

• Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, 16 Dorodna Str., 03-195 Warsaw, Poland, Tel.: [phone], Fax: [phone]

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