Chromatin maintenance by a molecular motor protein

Chromokinesins in Genome Maintenance and Cancer

“…It is intriguing that condensin II, with which KIF4 interacts, is required for initiation of chromatin reorganization and resolution of duplicated sister chromatids during S-phase [ 74 ]. The observation that loss of KIF4 results in premature chromosome condensation [ 11 ] is consistent with the fact that S-phase assembly is affected and progression through S-phase is delayed due to loss of KIF4 [ 36 ]. It is tantalizing to speculate that KIF4, in collaboration with condensin and other chromatin protein complexes, plays a fundamental role not only in shaping the mitotic chromosome structure, but also in global genome organization during interphase, and particularly in S-phase chromosome organization [ 36 ].…”

“…Likely as a functional consequence of these defects, normally silenced satellite repeat elements are highly expressed and global gene expression is misregulated upon KIF4 depletion [ 36 ]. Furthermore, DNA replication is substantially slowed down in the absence of KIF4 and several histone chaperones, chromatin remodeling and assembly proteins with which KIF4 interacts, such as Asf1 and RbAp48, fail to be recruited to replicated chromosomes [ 36 ]. Histone chaperones have also been shown to regulate the localization of important chromatin modifying enzymes.…”

“…Furthermore, morphologically discernible heterochromatin blocks and peripheral heterochromatin are conspicuously absent from cells lacking KIF4 and global chromatin structure assumes a largely "open" confi guration [ 36 ]. Likely as a functional consequence of these defects, normally silenced satellite repeat elements are highly expressed and global gene expression is misregulated upon KIF4 depletion [ 36 ]. Furthermore, DNA replication is substantially slowed down in the absence of KIF4 and several histone chaperones, chromatin remodeling and assembly proteins with which KIF4 interacts, such as Asf1 and RbAp48, fail to be recruited to replicated chromosomes [ 36 ].…”

“…Given their prominent nuclear localization during interphase, it is intriguing to speculate that chromokinesins contribute to the maintenance of mammalian nuclear architecture [ 36 ]. In support of such a role, KIF4 interacts with DNA and several chromatin-associated proteins including chromatin assembly factors Asf1, RbAp 48 and PARP-1 during interphase [ 36 ].…”

“…In support of such a role, KIF4 interacts with DNA and several chromatin-associated proteins including chromatin assembly factors Asf1, RbAp 48 and PARP-1 during interphase [ 36 ]. Furthermore, morphologically discernible heterochromatin blocks and peripheral heterochromatin are conspicuously absent from cells lacking KIF4 and global chromatin structure assumes a largely "open" confi guration [ 36 ]. Likely as a functional consequence of these defects, normally silenced satellite repeat elements are highly expressed and global gene expression is misregulated upon KIF4 depletion [ 36 ].…”