Editing Spindle checkpoint (section)

===== The role of heterochromatin =====
Classical cytologic observations suggested that sister chromatids are more strongly attached at [[heterochromatin|heterochromatic]] regions,<ref name="Gonzalez91">{{cite journal | vauthors = Gonzalez C, Casal Jimenez J, Ripoll P, Sunkel CE | title = The spindle is required for the process of sister chromatid separation in Drosophila neuroblasts | journal = Experimental Cell Research | volume = 192 | issue = 1 | pages = 10–5 | date = January 1991 | pmid = 1898588 | doi = 10.1016/0014-4827(91)90150-S }}</ref> and this suggested that the special structure or composition of heterochromatin might favour cohesin recruitment.<ref name="Losada2001b">{{cite journal | vauthors = Losada A, Hirano T | title = Shaping the metaphase chromosome: coordination of cohesion and condensation | journal = BioEssays | volume = 23 | issue = 10 | pages = 924–35 | date = October 2001 | pmid = 11598959 | doi = 10.1002/bies.1133 | s2cid = 31210810 }}</ref> In fact, it has been shown that Swi6 (the homolog of HP-1 in ''S. pombe'') binds to methylated [[lysine|Lys]] 9 of [[histone]] H3 and promotes the binding of cohesin to the centromeric repeats in ''S. pombe''.<ref name="Bernard2001">{{cite journal | vauthors = Bernard P, Maure JF, Partridge JF, Genier S, Javerzat JP, Allshire RC | title = Requirement of heterochromatin for cohesion at centromeres | journal = Science | volume = 294 | issue = 5551 | pages = 2539–42 | date = December 2001 | pmid = 11598266 | doi = 10.1126/science.1064027 | bibcode = 2001Sci...294.2539B | s2cid = 31166180 }}</ref><ref name="Nonaka2002">{{cite journal | vauthors = Nonaka N, Kitajima T, Yokobayashi S, Xiao G, Yamamoto M, Grewal SI, Watanabe Y | title = Recruitment of cohesin to heterochromatic regions by Swi6/HP1 in fission yeast | journal = Nature Cell Biology | volume = 4 | issue = 1 | pages = 89–93 | date = January 2002 | pmid = 11780129 | doi = 10.1038/ncb739 | s2cid = 23036084 | doi-access = free }}</ref> More recent studies indicate that the [[RNAi]] machinery regulates heterochromatin establishment, which in turn recruits cohesin to this region, both in ''S. pombe''<ref name="Hall2003">{{cite journal | vauthors = Hall IM, Noma K, Grewal SI | title = RNA interference machinery regulates chromosome dynamics during mitosis and meiosis in fission yeast | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 1 | pages = 193–8 | date = January 2003 | pmid = 12509501 | pmc = 140924 | doi = 10.1073/pnas.232688099 | bibcode = 2003PNAS..100..193H | doi-access = free }}</ref> and in vertebrate cells.<ref name="Fukagawa2004">{{cite journal | vauthors = Fukagawa T, Nogami M, Yoshikawa M, Ikeno M, Okazaki T, Takami Y, Nakayama T, Oshimura M | title = Dicer is essential for formation of the heterochromatin structure in vertebrate cells | journal = Nature Cell Biology | volume = 6 | issue = 8 | pages = 784–91 | date = August 2004 | pmid = 15247924 | doi = 10.1038/ncb1155 | s2cid = 24798145 }}</ref>  However, there must be other mechanisms than heterochromatin to ensure an augmented cohesion at centromeres, because ''S. cerevisiae'' lacks heterochromatin next to centromeres, but the presence of a functional centromere induces an increase of cohesin association in a contiguous region, spanning 20-50kb.<ref name="Weber2004">{{cite journal | vauthors = Weber SA, Gerton JL, Polancic JE, DeRisi JL, Koshland D, Megee PC | title = The kinetochore is an enhancer of pericentric cohesin binding | journal = PLOS Biology | volume = 2 | issue = 9 | pages = E260 | date = September 2004 | pmid = 15309047 | pmc = 490027 | doi = 10.1371/journal.pbio.0020260 | doi-access = free }} {{open access}}</ref>

In this direction, '''Orc2''' (one protein included in the [[origin recognition complex]], ORC, implicated in the initiation of [[DNA replication]] during [[S phase]]) is also located on kinetochores during mitosis in human cells;<ref name=Prasanth2004>{{cite journal | vauthors = Prasanth SG, Prasanth KV, Siddiqui K, Spector DL, Stillman B | title = Human Orc2 localizes to centrosomes, centromeres and heterochromatin during chromosome inheritance | journal = The EMBO Journal | volume = 23 | issue = 13 | pages = 2651–63 | date = July 2004 | pmid = 15215892 | pmc = 449767 | doi = 10.1038/sj.emboj.7600255 }}</ref> in agreement with this localization, some observations indicate that Orc2 in yeast is implicated in sister chromatid cohesion, and its removal induces SAC activation.<ref name=Shimada2007>{{cite journal | vauthors = Shimada K, Gasser SM | title = The origin recognition complex functions in sister-chromatid cohesion in Saccharomyces cerevisiae | journal = Cell | volume = 128 | issue = 1 | pages = 85–99 | date = January 2007 | pmid = 17218257 | doi = 10.1016/j.cell.2006.11.045 | doi-access = free }}</ref> It has also been observed that other components of the ORC complex (such as orc5 in ''S. pombe'') are implicated in cohesion.<ref name=Kato2008>{{cite journal | vauthors = Kato H, Matsunaga F, Miyazaki S, Yin L, D'Urso G, Tanaka K, Murakami Y | title = Schizosaccharomyces pombe Orc5 plays multiple roles in the maintenance of genome stability throughout the cell cycle | journal = Cell Cycle | volume = 7 | issue = 8 | pages = 1085–96 | date = April 2008 | pmid = 18414064 | doi = 10.4161/cc.7.8.5710 | doi-access = free }}</ref> However, the molecular pathway involving the ORC proteins seems to be additive to the cohesins' pathway, and it is mostly unknown.