Etudes sur le mécanisme de remodelage des nucléosomes par ...

tel-00413908, version 1 - 7 Sep 2009
translational repositioning is required for generation of remosomes, it could help in
maintaining the positional memory for the nucleosomes while still allowing factor access to
nucleosomal DNA.
Probably, the most interesting property of remosomes observed here is the random
distribution of accessibility. This feature can be especially important for repair of DNA
lesions encountered due to ionizing radiations or reactive oxygen species generated through
the cell metabolism itself which are random in nature. It is established that organization of
DNA into nucleosomes poses a strong barrier to these processes (Menoni et al., 2007). The
inherent random distribution of factor accessibility of remosomes could help in overcoming
this problem and possibly represent a major way of DNA repair in vivo. One may imagine
that stochastic generation of remosomes is a necessary step for initiating global genome repair
(GBR) by facilitating the initial recognition and binding of DNA glycosylases, the first
enzymes in base excision repair. We plan, at least for the moment, to study the role
remosomes in repair by a series of in vitro experiments.
In addition, we will also study how transcription factors can invade the nucleosome. The
expectation is that within the remosomes, in contrast to conventional nucleosomes, the histone
octamer would become “invisible” for transcription factors, i.e. the transcription factors
would be able to invade the remosome with affinity very similar to that of naked DNA. If this
is the case, the generation of remosomes would be a key factor in transcriptional regulation.
Are remosomes also formed upon nucleosome remodeling by other remodelers, belonging to
the three other families, different from that of SWI/SNF family? If yes, what are their
structures? Are they different or very close to those of the SWI/SNF and RSC generated
remosomes? Do histone chaperones or other proteins with co-remodeling activity affect
remosome formation? If yes, how do they do this?
The discovery of remosomes has presented a multitude of question of which only a part were
enumerated above. Addressing these questions remains a challenge for future studies.
161