Soon after cohesin was described as this guardian of
sister chromatid cohesion, it also became clear that there is just more to it.
The main focus of our research is to understand the regulation of gene expression by cohesin and related proteins, which are also required for sister
chromatid cohesion during mitosis (see «Background»).
The meiosis I — specific monopolin complex helps to keep sister
chromatids together in the first meiotic division.
Csm1 point - mutations that disrupt kinetochore - subunit binding also disrupt sister
chromatid co-orientation in S. cerevisiae meiosis I.
It rapidly assembles when cells enter mitosis, and it disassembles, after sister
chromatid separation and mitotic exit.
Examples of chromosomes with extra links
between chromatids, comparing with a normal chromosome (on the left).
As you can see, during the 24 hours of a typical mammalian cell cycle, cohesin is pretty much always directly associated with the entire genome (the exceptions being chromosomes arms during most of mitosis, i.e. 20 - 40 minutes and entire
chromatids during anaphase, i.e. ~ 10 minutes).
In the second stage of meiosis, the single pairs of chromosomes — two sister
chromatids joined in the middle — separate and the egg cell divides again in the same way, leaving a single mature egg cell with one copy of each chromosome.
The findings of this research, carried out by Sandra Muñoz Galván, María Luisa García Rubio, Pedro Ortega, José Francisco Ruiz, Sonia Jimeno, Benjamín Pardo, Belén Gómez González and Andrés Aguilera, have been brought together in the article A new role for Rrm3 in repair of replication - born DNA breakage by sister
chromatid recombination published by the review PLoS Genet in its May 2017 edition.
The
mutant chromatids failed to separate completely at the midzone, becoming stretched to up to twice their normal length.
Mechanistically, inhibition of SA1 in the SA2 - mutated cells led to
premature chromatid separation, dramatic extension of mitotic duration, and consequently lethal failure of cell division.
There is good evidence that initial cohesin loading is already topological (meaning, the ring closes around the
single chromatid).
According to our current understanding, cohesin is already loaded onto DNA (along the entire length of the decondensed one -
chromatid chromosome) in telophase, i.e. only minutes after chromosome segregation, by opening / closing its Smc1 - Smc3 interaction site (or «entry gate»).
This not only ensures that sister
chromatids remain cohesed until the metaphase - to - anaphase transition, but also provides us with the stereotypical image of an X-shaped chromosome.
Cohesin's integral ring structure is composed of three proteins: Smc1, Smc3 (Structural maintenance of chromosomes), and Scc1 / Rad21 (Sister
chromatid cohesin / radiation sensitive).
The role of DNA topology in holding sister
chromatids together before anaphase was investigated by analyzing the structure of a small circular minichromosome in cell cycle (cdc) mutants of the yeast Saccharomyces cerevisiae.
The first project aims at understanding the contribution of SMC (structural maintenance of chromosomes) proteins and their complexes to essential processes in mitosis and meiosis such as sister
chromatid cohesion and segregation, DNA recombination and repair, chromosome structure and behaviour.
We propose that Csm1 / Lrs4 functions as a molecular clamp, crosslinking kinetochore components to enforce sister
chromatid co-orientation in S. cerevisiae meiosis I and to suppress merotelic attachment in S. pombe mitosis, and crosslinking rDNA repeats to aid rDNA silencing.
NIPBL, encoding a homolog of fungal Scc2 - type
sister chromatid cohesion proteins and fly Nipped - B, is mutated in Cornelia de Lange syndrome
Therefore, sister minichromosome molecules need not remain topologically interlocked until anaphase in order to be properly segregated, and topological interlocking of sister DNA molecules apparently is not the primary force holding sister
chromatids together.
Telomeres are the structures that cap each end of
a chromatid, at the extreme end of the chromosomal DNA.
During cell division, chromosomes acquire a characteristic X-shape with the two DNA molecules (sister
chromatids) linked at a central «connection region» that contains highly compacted DNA.
Their results indicated that the inappropriate location of these chromosomal regions is sufficient to load the cohesion «glue,» leading to the formation of additional connections between sister -
chromatids.
As cell division proceeds and the sister
chromatids are pulled to opposite poles of the cell, the presence of these extra cohesion sites leads to abnormal chromosome stretching as it is harder to «unglue» the chromatids.
The key to understand this problem lies on the «glue» that keeps the two sister
chromatids together.
(E) Balanced predivision of sister
chromatids (red and purple arrows).
«What we found,» explains team leader Tomoya Kitajima, «is that in older cells, the bivalents sometimes separate early, and this leads to division of sister
chromatids in the first stage of meiosis, rather than in the second stage.»
Closer examination of the chromosome - tracking data showed that the dominant type of error was predivision of sister
chromatids, and not movement of intact chromosome pairs to only one of the new cells.
The maintenance of telomeres — the structures of repetitive sequences at the end of
a chromatid — is essential to the health of a cell.
In addition to binding microtubules, centromeres have other functions, including sister
chromatid cohesion and preventing microtubules from both poles attaching to the same chromatid.
In our studies on germ cells, we identified a novel SMC protein that in a mouse model turned out to be essential for meiotic sister
chromatid cohesion, telomere integrity, and chromosome structure.
From S - phase onward, the two copies of each chromosome (referred to as sister
chromatids) are connected by molecular rings and each copy attempts to establish attachments to spindle microtubules that emanate from two spindle poles.
The monopolin complex regulates different types of kinetochore - microtubule attachments in fungi, ensuring sister
chromatid co-orientation in Saccharomyces cerevisiae meiosis I and inhibiting merotelic attachment in Schizosaccharomyces pombe mitosis.
Cohesin obviously gets its name from the fact that it causes «cohesion» between sister
chromatids, which has been first described 20 years ago in budding yeast.
When the second sister
chromatid is synthesized in S phase, cohesin establishes sister chromatid cohesion in a co-replicative manner (only after you have the second sister chromatid, you can actually start talking about «cohesion»).
Here, the ring complex is thought to help CTCF's agenda by creating internal loops, i.e. inside the same sister
chromatid!
It is important to mention that cohesin also has a very unique role in meiosis where it not only coheses sister
chromatids but also chromosomal homologs (the two maternal / paternal versions of a chromosome, each consisting of two sisters, which themselves are cohesed).
To recap, cohesin is a multimeric ring complex, which holds the two
chromatids of a chromosome together from the time the second sister chromatid is generated in S phase until their separation in M phase.
Meiotic cohesin STAG3 is required for chromosome axis formation and sister
chromatid cohesion.
Simultaneously, cohesin's job is to take those newly generated sister
chromatids and hold them tightly to the old one.