Chromatin Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important ...

assembly factor-1 (CAF-1) is a

protein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain. Protein ...

— including

Chaf1a Chromatin assembly factor 1 subunit A is a protein that in humans is encoded by the ''CHAF1A'' gene. Function Chromatin assembly factor I (CAF-1) is a nuclear complex consisting of p50, p60 (CHAF1B; MIM 601245), and p150 (CHAF1A) subunits that ...

(p150),

Chaf1b Chromatin assembly factor 1 subunit B is a protein that in humans is encoded by the ''CHAF1B'' gene. Function Chromatin assembly factor I (CAF-1) is required for the assembly of histone octamers onto newly-replicated DNA. CAF-I is composed of ...

(p60), and p48 subunits in humans, or Cac1, Cac2, and Cac3, respectively, in yeast— that assembles

histone In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn a ...

tetramers onto replicating DNA during the S phase of the cell cycle.

Function

CAF-1 functions as a histone chaperone that mediates the first step in

nucleosome A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundame ...

formation by tetramerizing and depositing newly synthesized histone H3/ H4 onto DNA rapidly behind

replication fork In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritan ...

s. H3 and H4 are synthesized in the cytoplasm. Several studies have shown that the interaction between CAF-1 and PCNA (proliferating cell nuclear antigen, which stabilizes CAF-1 at replication forks, is important for CAF-1's role in nucleosome assembly The three subunits work together to make the complex function. The human subunit (p150) interacts with PCNA, which acts as a sliding clamp, to help the CAF-1 complex interact with the DNA replication fork. Additionally, p150 along with PCNA performs nucleotide excision repair to fix any damaged DNA. P60 interacts with ASF1a/b, which is a histone chaperone for H3/H4. p48 has roles outside of CAF-1, but when involved with the complex, it binds to H4. p60 attracts ASF1a/b which is a chaperone for H3/H4 and this is in the complex with p150 which interacts with PCNA to attach to the replication fork. The CAF-1 complex adds the histones to the DNA ahead of the replication fork. A mutation in p150 that results in a loss of function would lead to double stranded breaks, interruptions in the replication fork and translocations. In p60, loss of function would mean the histone chaperone for H3/H4 would not interact with the complex. A mutation like this in either subunit would result in loss of function for the CAF-1 complex as a whole. However, loss of function in p48 would alter how well the complex is able to chaperone chromatin, but would not stop it as a whole.

Roles

CAF-1 is required for the spatial organization and

epigenetic In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are ...

marking of

heterochromatin Heterochromatin is a tightly packed form of DNA or '' condensed DNA'', which comes in multiple varieties. These varieties lie on a continue between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a rol ...

domains in pluripotent embryonic cells, creating a cellular memory of

somatic cell A somatic cell (from Ancient Greek σῶμα ''sôma'', meaning "body"), or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Such cells com ...

identity during

cellular differentiation Cellular differentiation is the process in which a stem cell alters from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular ...

. Cells resembling 2-cell-stage mouse embryos (

totipotent Pluripotency: These are the cells that can generate into any of the three Germ layers which imply Endodermal, Mesodermal, and Ectodermal cells except tissues like the placenta. According to Latin terms, Pluripotentia means the ability for many thin ...

cells) can be induced in vitro through downregulation of the chromatin-assembly activity of CAF-1 in

embryonic stem cell Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre- implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist ...

s. CAF-1 forms a deadenylase complex with

CCR4-Not Carbon Catabolite Repression—Negative On TATA-less, or CCR4-Not, is a multiprotein complex that functions in gene expression. The complex has multiple enzymatic activities as both a poly(A) 3′-5′ exonuclease and a ubiquitin ligase. The com ...

, which should not be confused with the unrelated

CCR4 C-C chemokine receptor type 4 is a protein that in humans is encoded by the ''CCR4'' gene. CCR4 has also recently been designated CD194 (cluster of differentiation 194). The protein encoded by this gene belongs to the G protein-coupled receptor f ...

. The CAF-1/CCR4-Not complex cooperates with the

release factor A release factor is a protein that allows for the termination of translation by recognizing the termination codon or stop codon in an mRNA sequence. They are named so because they release new peptides from the ribosome. Background During t ...

eRF3 and

PABPC1 Polyadenylate-binding protein 1 is a protein that in humans is encoded by the ''PABPC1'' gene. The protein PABP1 binds mRNA and facilitates a variety of functions such as transport into and out of the nucleus, degradation, translation, and stabili ...

to shorten the poly(A) tail of

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...

during translation.

Function

Roles

References

Further reading