The role of DNA damage in cellular senescence

Abstract

Cells grown in vitro may be introduced into terminal growth arrest termed cellular senescence. In normal cells, it always arises when they reach the end of their proliferative capacity. However, this process may be also caused by various means anytime during the cultivation of both normal and at some circumstances also in immortal cells. Current view of cellular senescence places this phenomenon into direct relationship with DNA damage. The first aim of this study is to elucidate the role of DNA damage in chemically induced senescence. Until recently, DNA damage was not studied in this particular model. All chemicals used in this work are routinely used to unveil unstable parts of the human genome, so called fragile sites, which are inherently prone to DNA breakage. The second aim of this study is to asses the possibility that these sensitive regions of DNA might be also involved in senescent phenotype. Two of the three chemicals used in this study, 5-bromodeoxyuridine and distamycin A, were commonly used to accomplish senescence, and their effect on main senescence-associated changes in cellular proteome is thus relatively well defined. The changes caused by the third compound, thymidine, were so far poorly investigated. Therefore, the last aim of this work is to find out, if the changes of protein...

Cells grown in vitro may be introduced into terminal growth arrest termed cellular senescence. In normal cells, it always arises when they reach the end of their proliferative capacity. However, this process may be also caused by various means anytime during the cultivation of both normal and at some circumstances also in immortal cells. Current view of cellular senescence places this phenomenon into direct relationship with DNA damage. The first aim of this study is to elucidate the role of DNA damage in chemically induced senescence. Until recently, DNA damage was not studied in this particular model. All chemicals used in this work are routinely used to unveil unstable parts of the human genome, so called fragile sites, which are inherently prone to DNA breakage. The second aim of this study is to asses the possibility that these sensitive regions of DNA might be also involved in senescent phenotype. Two of the three chemicals used in this study, 5-bromodeoxyuridine and distamycin A, were commonly used to accomplish senescence, and their effect on main senescence-associated changes in cellular proteome is thus relatively well defined. The changes caused by the third compound, thymidine, were so far poorly investigated. Therefore, the last aim of this work is to find out, if the changes of protein...