Cohesin in cancer: chromosome segregation and beyond

Cohesin is an evolutionarily conserved, four-subunit complex that entraps DNA fibres within its ring-shaped structure. It was originally identified and named for its role in mediating sister chromatid cohesion, which is essential for chromosome segregation and DNA repair. Increasing evidence indicates that cohesin participates in other processes that involve DNA looping, most importantly, transcriptional regulation. Mutations in genes encoding cohesin subunits and other regulators of the complex have recently been identified in several types of tumours. Whether aneuploidy that results from chromosome missegregation is the major contribution of cohesin mutations to cancer progression is under debate.

[1]  K. Monahan,et al.  Role of CCCTC binding factor (CTCF) and cohesin in the generation of single-cell diversity of Protocadherin-α gene expression , 2012, Proceedings of the National Academy of Sciences.

[2]  F. Uhlmann,et al.  Biochemical reconstitution of topological DNA binding by the cohesin ring , 2013, Nature.

[3]  S. Gabriel,et al.  Discovery and saturation analysis of cancer genes across 21 tumor types , 2014, Nature.

[4]  M. Blasco,et al.  Cohesin‐SA1 deficiency drives aneuploidy and tumourigenesis in mice due to impaired replication of telomeres , 2012, The EMBO journal.

[5]  The Cancer Genome Atlas Research Network,et al.  Comprehensive molecular characterization of urothelial bladder carcinoma , 2014, Nature.

[6]  Masao Nagasaki,et al.  Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms , 2012, Nature Genetics.

[7]  A. Lander,et al.  Reduction of Nipbl impairs cohesin loading locally and affects transcription but not cohesion-dependent functions in a mouse model of Cornelia de Lange Syndrome. , 2013, Biochimica et biophysica acta.

[8]  Replication stress links structural and numerical cancer chromosomal instability (vol 494, pg 492, 2013) , 2013 .

[9]  S. Miyano,et al.  The landscape of somatic mutations in Down syndrome–related myeloid disorders , 2013, Nature Genetics.

[10]  Hongtao Yu,et al.  Mutational Inactivation of STAG2 Causes Aneuploidy in Human Cancer , 2011, Science.

[11]  I. Krantz,et al.  Cornelia de Lange syndrome, cohesin, and beyond , 2009, Clinical genetics.

[12]  J. Peters,et al.  Aurora B and Cdk1 mediate Wapl activation and release of acetylated cohesin from chromosomes by phosphorylating Sororin , 2013, Proceedings of the National Academy of Sciences.

[13]  D. Cleveland,et al.  Losing balance: the origin and impact of aneuploidy in cancer , 2012, EMBO reports.

[14]  L. Schöckel,et al.  Cleavage of cohesin rings coordinates the separation of centrioles and chromatids , 2011, Nature Cell Biology.

[15]  R. Benezra,et al.  The cancer biology of whole-chromosome instability , 2013, Oncogene.

[16]  K. Döhner,et al.  Mutations in the cohesin complex in acute myeloid leukemia: clinical and prognostic implications. , 2014, Blood.

[17]  Steven J. M. Jones,et al.  Comprehensive molecular characterization of urothelial bladder carcinoma , 2014, Nature.

[18]  P. Black.  Frequent truncating mutations of STAG2 in bladder cancer. , 2014, Urology.

[19]  Petra C. Schwalie,et al.  A CTCF-independent role for cohesin in tissue-specific transcription. , 2010, Genome research.

[20]  M. Groudine,et al.  Cohesin Mediates Chromatin Interactions That Regulate Mammalian β-globin Expression* , 2011, The Journal of Biological Chemistry.

[21]  J. Dekker,et al.  The hierarchy of the 3D genome. , 2013, Molecular cell.

[22]  J. Ellenberg,et al.  Wapl is an essential regulator of chromatin structure and chromosome segregation , 2013, Nature.

[23]  Susan Smith,et al.  Differential regulation of telomere and centromere cohesion by the Scc3 homologues SA1 and SA2, respectively, in human cells , 2009, The Journal of cell biology.

[24]  Huanming Yang,et al.  Whole-genome and whole-exome sequencing of bladder cancer identifies frequent alterations in genes involved in sister chromatid cohesion and segregation , 2013, Nature Genetics.

[25]  V. Guacci,et al.  Systematic Reduction of Cohesin Differentially Affects Chromosome Segregation, Condensation, and DNA Repair , 2010, Current Biology.

[26]  G. Schroth,et al.  Cohesin-mediated interactions organize chromosomal domain architecture , 2013, The EMBO journal.

[27]  Joshua F. McMichael,et al.  The Origin and Evolution of Mutations in Acute Myeloid Leukemia , 2012, Cell.

[28]  A. Hyman,et al.  Sororin Mediates Sister Chromatid Cohesion by Antagonizing Wapl , 2010, Cell.

[29]  G. Parmigiani,et al.  Chromatid cohesion defects may underlie chromosome instability in human colorectal cancers , 2008, Proceedings of the National Academy of Sciences.

[30]  Jesse R. Dixon,et al.  Cohesin and CTCF differentially affect chromatin architecture and gene expression in human cells , 2013, Proceedings of the National Academy of Sciences.

[31]  H. Aburatani,et al.  Cohesin mediates transcriptional insulation by CCCTC-binding factor , 2008, Nature.

[32]  David A. Orlando,et al.  Mediator and Cohesin Connect Gene Expression and Chromatin Architecture , 2010, Nature.

[33]  E. Nigg,et al.  Centromere DNA decatenation depends on cohesin removal and is required for mammalian cell division , 2010, Journal of Cell Science.

[34]  Jiri Bartek,et al.  Replication stress links structural and numerical cancer chromosomal instability , 2013, Nature.

[35]  J. Malaterre,et al.  Rad21-Cohesin Haploinsufficiency Impedes DNA Repair and Enhances Gastrointestinal Radiosensitivity in Mice , 2010, PloS one.

[36]  A. Losada,et al.  Cohesin, a chromatin engagement ring. , 2013, Current opinion in cell biology.

[37]  Daniel Rico,et al.  Cohesin organizes chromatin loops at DNA replication factories. , 2010, Genes & development.

[38]  J. Stamatoyannopoulos,et al.  Human mutation rate associated with DNA replication timing , 2009, Nature Genetics.

[39]  A. Losada,et al.  Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres , 2013, The EMBO journal.

[40]  Gabriele Gillessen-Kaesbach,et al.  HDAC8 mutations in Cornelia de Lange Syndrome affect the cohesin acetylation cycle , 2012, Nature.

[41]  Kim Nasmyth,et al.  Molecular architecture of SMC proteins and the yeast cohesin complex. , 2002, Molecular cell.

[42]  V. Pubul Núñez,et al.  [Clinical and prognostic implications of age in acute myocardial infarct]. , 1991, Archivos del Instituto de Cardiologia de Mexico.

[43]  David J. Reiss,et al.  CTCF physically links cohesin to chromatin , 2008, Proceedings of the National Academy of Sciences.

[44]  C. Taylor,et al.  Frequent inactivating mutations of STAG2 in bladder cancer are associated with low tumour grade and stage and inversely related to chromosomal copy number changes , 2013, Human molecular genetics.

[45]  J. Ellenberg,et al.  Live-Cell Imaging Reveals a Stable Cohesin-Chromatin Interaction after but Not before DNA Replication , 2006, Current Biology.

[46]  A. Valencia,et al.  Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy , 2013, Nature Genetics.

[47]  D. Pisano,et al.  A unique role of cohesin‐SA1 in gene regulation and development , 2012, The EMBO journal.