The acetyltransferase Eco1 elicits cohesin dimerization during S phase

Shi, Di; Zhao, Shuaijun; Zuo, Mei-Qing; Zhang, Jingjing; Hou, Wenya; Dong, Meng‐Qiu; Cao, Qinhong; Lou, Huiqiang

doi:10.1074/jbc.ra120.013102

Cited by 17 publications

(15 citation statements)

References 52 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mechanistically, the acetylation of Smc3 inhibits both the ATPase activity of cohesin and conformational changes (Camdere et al, 2018). Recently, it has been suggested that acetylation also induces cohesin dimerization (Shi et al, 2020a). Either way, we suggest that, as a result of the acetylation, cohesin loop extrusion is fully turned off, likely by modifying the ATPase activity at the SMC head.…”

Section: Molecular Switches For Turning Off Loop Extrusionmentioning

confidence: 71%

Hit the brakes – a new perspective on the loop extrusion mechanism of cohesin and other SMC complexes

Matityahu

Onn

2021

Journal of Cell Science

View full text Add to dashboard Cite

The three-dimensional structure of chromatin is determined by the action of protein complexes of the structural maintenance of chromosome (SMC) family. Eukaryotic cells contain three SMC complexes, cohesin, condensin, and a complex of Smc5 and Smc6. Initially, cohesin was linked to sister chromatid cohesion, the process that ensures the fidelity of chromosome segregation in mitosis. In recent years, a second function in the organization of interphase chromatin into topologically associated domains has been determined, and loop extrusion has emerged as the leading mechanism of this process. Interestingly, fundamental mechanistic differences exist between mitotic tethering and loop extrusion. As distinct molecular switches that aim to suppress loop extrusion in different biological contexts have been identified, we hypothesize here that loop extrusion is the default biochemical activity of cohesin and that its suppression shifts cohesin into a tethering mode. With this model, we aim to provide an explanation for how loop extrusion and tethering can coexist in a single cohesin complex and also apply it to the other eukaryotic SMC complexes, describing both similarities and differences between them. Finally, we present model-derived molecular predictions that can be tested experimentally, thus offering a new perspective on the mechanisms by which SMC complexes shape the higher-order structure of chromatin.

show abstract

Section: Molecular Switches For Turning Off Loop Extrusionmentioning

confidence: 71%

Hit the brakes – a new perspective on the loop extrusion mechanism of cohesin and other SMC complexes

Matityahu

Onn

2021

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…After proofreading cohesin stops at the opposite side of a TAD loop and then induces proofreading of SAT domain by another complex (SMS5/6) in a relay race mechanism. However, it should be taken into account that 20% of cohesin (SMC complex) does not move; it forms cohesin dimers that keep sister chromatids together (Shi et al, 2020) ("cohesin" in a true sense).…”

Section: Structure Of Tad Anchorsmentioning

confidence: 99%

Chromosome instability induced by mutations in TAD anchors leads to tumors

Luchnik

2021

GENOME INSTAB. DIS.

View full text Add to dashboard Cite

In the light of recent data, a way is described between mutations in TAD anchors and stimulation of tumor growth driven by chromosome instability. At the end of this way every tumor sacrifices by a portion of its cells, dying necrotically, to stimulate remaining cells to proliferate. Necrosis (cell puncture and leakage of chemokine CXCL12) launches the mechanism of wound healing that stimulates cells to divide. Necrosis in cancer cells is induced by chromosome aberrations hindering anaphase cleavage furrow ingression and leading to membrane rupture. Inherited chromosome instability arises, because some of DNA loops (gene blocks, also called TADs) are torn off chromatid axes at their attachment points (anchors) because of mutations at some of these points. Namely, CTCF target sites (CCXXXAGG GGG ) at the basements of TAD loops acquire mutations in central Adenine and in 3-5 nucleotides just beyond the borders of this 11 bp sequence. The sequence itself is degenerate between different TADs mainly at the X nucleotides, rarely at some others. Interstitial satellite DNA (SAT) adjacent to TADs anchors begins to behave such as telomeric satellite DNA. This launches transcription of such erupted satellites not leaned against TADs and production of their DNA copies due to the action of TERT reverse transcriptase just like in telomeres and leads to insertion of telomere sequences into such SATs. Some sticky ends in satellites also add to chromosome instability.

show abstract

“…Recently, the inter-allelic complementation between defective Scc1 and Smc3 alleles has provided evidence that multiple cohesin subunits can interact with each other on the chromatin [193,194]. Indeed, many biochemical studies have confirmed that cohesin can form clusters or dimers in vivo [195,196]. The exact mechanism of action is still debated (reviewed by [190]).…”

Section: Sister Chromatid Cohesionmentioning

confidence: 99%

PCNA Loaders and Unloaders—One Ring That Rules Them All

Arbel

Choudhary

Tfilin

et al. 2021

Genes

View full text Add to dashboard Cite

During each cell duplication, the entirety of the genomic DNA in every cell must be accurately and quickly copied. Given the short time available for the chore, the requirement of many proteins, and the daunting amount of DNA present, DNA replication poses a serious challenge to the cell. A high level of coordination between polymerases and other DNA and chromatin-interacting proteins is vital to complete this task. One of the most important proteins for maintaining such coordination is PCNA. PCNA is a multitasking protein that forms a homotrimeric ring that encircles the DNA. It serves as a processivity factor for DNA polymerases and acts as a landing platform for different proteins interacting with DNA and chromatin. Therefore, PCNA is a signaling hub that influences the rate and accuracy of DNA replication, regulates DNA damage repair, controls chromatin formation during the replication, and the proper segregation of the sister chromatids. With so many essential roles, PCNA recruitment and turnover on the chromatin is of utmost importance. Three different, conserved protein complexes are in charge of loading/unloading PCNA onto DNA. Replication factor C (RFC) is the canonical complex in charge of loading PCNA during the S-phase. The Ctf18 and Elg1 (ATAD5 in mammalian) proteins form complexes similar to RFC, with particular functions in the cell’s nucleus. Here we summarize our current knowledge about the roles of these important factors in yeast and mammals.

show abstract

The acetyltransferase Eco1 elicits cohesin dimerization during S phase

Cited by 17 publications

References 52 publications

Hit the brakes – a new perspective on the loop extrusion mechanism of cohesin and other SMC complexes

Hit the brakes – a new perspective on the loop extrusion mechanism of cohesin and other SMC complexes

Chromosome instability induced by mutations in TAD anchors leads to tumors

PCNA Loaders and Unloaders—One Ring That Rules Them All

Contact Info

Product

Resources

About