The role of chromatin proteins in DNA damage recognition and repair.
The structure of chromatin is the major factor determining the rate and efficiency of DNA repair. Chromatin remodeling events such as rearrangement of nucleosomes and higher order chromatin structures are indispensable features of repair processes. During the last decade numerous chromatin proteins have been identified that preferentially bind to different types of DNA damage. The HMGB proteins, which preferentially interact with DNA intrastrand crosslinks induced by cisplatin, are the archetypal example of such proteins. Several hypothetical models have been proposed describing the role of such damage-binding chromatin proteins. The damage shielding model postulates that binding of chromatin proteins to damaged DNA might disturb damage recognition by repair factors and impair its removal. Alternatively, the damage-recognition/signaling model proposes that the binding of specific chromatin proteins to damaged DNA could serve as a hallmark to be recognized by repair proteins. Additionally, the binding of specific chromatin proteins to damaged DNA could induce chromatin remodeling at the damage site and indirectly affect its repair. This paper aims to critically review current experimental data in relation to such possible roles of chromatin proteins.
Widlak
Piotr
P
Department of Experimental and Clinical Radiobiology, Maria Sklodowska-Curie Cancer Center and Institute of Oncology, Wybrzeze AK 15, 44-100, Gliwice, Poland. widlak@io.gliwice.pl
Pietrowska
Monika
M
Lanuszewska
Joanna
J
D000818:Animals; D002843:Chromatin / Q000502:physiology*; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D024002:HMGB Proteins / Q000378:metabolism; D006657:Histones / Q000235:genetics; D006801:Humans
D002843:Chromatin; C468783:H2AX protein, human; D024002:HMGB Proteins; D006657:Histones; D002945:Cisplatin