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Chromatin remodelling beyond transcription: the INO80 and SWR1 complexes

Key Points

  • ATP-dependent chromatin-remodelling complexes alter nucleosome composition and positioning to assist in DNA processing and metabolism.

  • The INO80 and SWR1 chromatin-remodelling complexes are highly conserved, and homologues have been identified in plants, flies, yeast and mammals.

  • The INO80 complex promotes nucleosome repositioning, or 'sliding', as well as histone eviction, which results in the complete removal of nucleosomes from the DNA.

  • The SWR1 complex facilitates histone exchange of the Htz1 (H2AZ in mammals) histone variant into the canonical nucleosome.

  • During activation of DNA damage response pathways, the INO80 and SWR1 complexes are recruited to chromatin regions at DNA damage sites through an interaction with phosphorylated H2AX. This interaction provides a mechanism to direct the chromatin-remodelling activities of the INO80 and SWR1 complexes to the DNA repair and cell cycle checkpoint pathways.

  • The INO80 and SWR1 complexes participate in a range of pathways involved in genome maintenance, such as DNA repair, checkpoint regulation, DNA replication, chromosome segregation and telomere stabilization.

  • Defects in the activities of the INO80 and SWR1 complexes result in genomic instability.

Abstract

Chromatin-modifying factors have essential roles in DNA processing pathways that dictate cellular functions. The ability of chromatin modifiers, including the INO80 and SWR1 chromatin-remodelling complexes, to regulate transcriptional processes is well established. However, recent studies reveal that the INO80 and SWR1 complexes have crucial functions in many other essential processes, including DNA repair, checkpoint regulation, DNA replication, telomere maintenance and chromosome segregation. During these diverse nuclear processes, the INO80 and SWR1 complexes function cooperatively with their histone substrates, γ-H2AX and H2AZ. This research reveals that INO80 and SWR1 ATP-dependent chromatin remodelling is an integral component of pathways that maintain genomic integrity.

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Figure 1: Chromatin-remodelling mechanisms of the INO80 and SWR1 complexes.
Figure 2: INO80 and SWR1 complexes regulate double-strand break repair.
Figure 3: The INO80 complex is a component of the Tel1 and Mec1 pathway.
Figure 4: The INO80 complex promotes recovery of stalled replication forks.
Figure 5: Regulation of ATP-dependent chromatin remodelling.

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Acknowledgements

The authors apologize for the omission of many interesting research articles that could not be described in this Review owing to the focused scope of the article and space limitations. We thank R. Herrera and J. Holcomb for assistance in developing figures. We also thank C. Wu for helpful discussions regarding the content of this manuscript. Funding for A.J.M. was provided by a National Institute of General Medical Sciences (NIGMS)-sponsored 'Pathways to Independence' K99 award.

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DATABASES

BioGRID — Repository for Interaction Datasets 

INO80

SWR1

SRCAP

Human Protein Reference Database 

BAF53A

RUVBL1

RUVBL2

SRCAP

UCH37

YY1

Saccharomyces Genome Database

Arp4

Arp6

ARP8

Ctf18

Ies3

Ies4

INO80

Ku70

Mec1

Nhp10

Rvb1

Rvb2

Swc2

Swc6

Swr1

Tel1

TOF1

FURTHER INFORMATION

Xuetong Shen's homepage

Ashby Morrison's homepage

Glossary

Helicase

An enzyme that unwinds double-stranded nucleic acids in an energy-dependent manner.

DEAD/H box

An evolutionarily conserved domain found in proteins that are a part of the super family 2 helicases, which are essential for RNA metabolism and processing.

RuvB

A bacterial ATP-dependent DNA helicase that forms a ring-shaped double hexamer complex around a Holliday junction and promotes its migration during homologous recombination.

Centromere

Region of a chromosome that is attached to the spindle during cell division.

HMG

(High mobility group). A large protein family of small, non-histone components of chromatin that function in chromatin structure.

Holliday junction

A mobile junction that contains four strands of DNA and is generated during the synaptic phase of homologous recombination.

Homologous recombination

A DNA recombination pathway, which includes the repair of double-strand DNA breaks, that uses a homologous double-stranded DNA as a template for the repair of the broken DNA.

Helicase-SANT-associated domain

The region in the ATPase subunit of the INO80 and SWI/SNF subfamilies that serves as the primary binding site for nuclear actin and actin-related proteins within the chromatin-remodelling complex.

Heterochromatin

Dense chromatin that is less transcriptionally active than euchromatin. Heterochromatin includes structural regions of the chromosome, such as centromeres and telomeres (constitutive heterochromatin), as well as genes that are silenced in a given cell type (facultative heterochromatin).

Non-homologous end joining

(NHEJ). A DNA repair pathway for double-strand breaks that is often error-prone because it leads to the joining of breaks without a template.

Mre11 nuclease

A subunit of the Mre11–Rad50–Xrs2 (MRX) complex that has 3′ to 5′ exonuclease activity and assists in resecting the DNA ends of a double-strand break.

Replication origin

A site where replication is initiated during S phase.

Replisome

A multiprotein complex at the junction of the DNA replication fork that contains all the enzymes that are required for DNA replication.

Kinetochore

A multiprotein complex that assembles on centromeric DNA and mediates the attachment and movement of chromosomes along the microtubules of the mitotic spindle.

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Morrison, A., Shen, X. Chromatin remodelling beyond transcription: the INO80 and SWR1 complexes. Nat Rev Mol Cell Biol 10, 373–384 (2009). https://doi.org/10.1038/nrm2693

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