Bloom syndrome protein is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''BLM''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
and is not expressed in
Bloom syndrome
Bloom syndrome (often abbreviated as BS in literature) is a rare autosomal recessive genetic disorder characterized by short stature, predisposition to the development of cancer, and genomic instability. BS is caused by mutations in the '' BLM'' ge ...
.
The Bloom syndrome gene product is related to the
RecQ subset of DExH box-containing DNA
helicase
Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separatin ...
s and has both DNA-stimulated
ATPase and ATP-dependent DNA helicase activities. Mutations causing
Bloom syndrome
Bloom syndrome (often abbreviated as BS in literature) is a rare autosomal recessive genetic disorder characterized by short stature, predisposition to the development of cancer, and genomic instability. BS is caused by mutations in the '' BLM'' ge ...
delete or alter helicase motifs and may disable the 3' → 5' helicase activity. The normal protein may act to suppress inappropriate
homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...
.
Meiosis
Recombination during
meiosis
Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately r ...
is often initiated by a DNA double-strand break (DSB). During recombination, sections of DNA at the
5' ends of the break are cut away in a process called resection. In the strand invasion step that follows, an overhanging
3' end
Directionality, in molecular biology and biochemistry, is the end-to-end chemical orientation of a single strand of nucleic acid. In a single strand of DNA or RNA, the chemical convention of naming carbon atoms in the nucleotide pentose-sugar-r ...
of the broken DNA molecule then "invades" the DNA of an homologous chromosome that is not broken. After strand invasion, the further sequence of events may follow either of two main pathways leading to a crossover (CO) or a non-crossover (NCO) recombinant (see
Genetic recombination and bottom of Figure in this section).
The budding yeast ''
Saccharomyces cerevisiae
''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...
'' encodes an ortholog of the Bloom syndrome (BLM) protein that is designated
Sgs1
Sgs1, also known as slow growth suppressor 1, is a DNA helicase protein found in ''Saccharomyces cerevisiae''. It is a homolog of the bacterial RecQ helicase. Like the other members of the RecQ helicase family, Sgs1 is important for DNA repair ...
(Small growth suppressor 1). Sgs1(BLM) is a
helicase
Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separatin ...
that functions in
homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may ...
al repair of DSBs. The
Sgs1
Sgs1, also known as slow growth suppressor 1, is a DNA helicase protein found in ''Saccharomyces cerevisiae''. It is a homolog of the bacterial RecQ helicase. Like the other members of the RecQ helicase family, Sgs1 is important for DNA repair ...
(BLM) helicase appears to be a central regulator of most of the recombination events that occur during ''S. cerevisiae''
meiosis
Meiosis (; , since it is a reductional division) is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, such as sperm or egg cells. It involves two rounds of division that ultimately r ...
.
During normal meiosis Sgs1(BLM) is responsible for directing recombination towards the alternate formation of either early NCOs or
Holliday junction joint molecules, the latter being subsequently resolved as COs.
In the plant ''
Arabidopsis thaliana'', homologs of the Sgs1(BLM) helicase act as major barriers to meiotic CO formation.
These helicases are thought to displace the invading strand allowing its annealing with the other 3’overhang end of the DSB, leading to NCO recombinant formation by a process called synthesis dependent strand annealing (SDSA) (see
Genetic recombination and Figure in this section). It is estimated that only about 4% of DSBs are repaired by CO recombination.
Sequela-Arnaud et al.
suggested that CO numbers are restricted because of the long-term costs of CO recombination, that is, the breaking up of favorable genetic combinations of alleles built up by past
natural selection
Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the heritable traits characteristic of a population over generations. Cha ...
.
Interactions
Bloom syndrome protein has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with:
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ATM,
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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 ...
,
*
CHEK1
Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the ''CHEK1'' gene. Chk1 coordinates the DNA damage response (DDR) and cell cycle checkpoint response. Activation of C ...
,
*
FANCM,
*
FEN1
Flap endonuclease 1 is an enzyme that in humans is encoded by the ''FEN1'' gene.
Function
The protein encoded by this gene removes 5' overhanging "flaps" (or short sections of single stranded DNA that "hang off" because their nucleotide bases a ...
,
*
H2AFX
H2A histone family member X (usually abbreviated as H2AX) is a type of histone protein from the H2A family encoded by the ''H2AFX'' gene. An important phosphorylated form is γH2AX (S139), which forms when double-strand breaks appear.
In humans ...
,
[
* MLH1]
* P53
p53, also known as Tumor protein P53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory protein that is often mutated in human cancers. The p53 proteins (originally thought to be, and often s ...
,
* RAD51L3
DNA repair protein RAD51 homolog 4 is a protein that in humans is encoded by the ''RAD51L3'' gene.
Function
The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and ...
,
* RAD51,
* RPA1
Replication protein A 70 kDa DNA-binding subunit is a protein that in humans is encoded by the ''RPA1'' gene.
Interactions
Replication protein A1 has been shown to interact with:
* BRCA2,
* BLM,
* MCM2,
* MCM4,
* MCM6,
* MCM7,
* MUTYH, ...
,
* TOP3A
DNA topoisomerase 3-alpha is an enzyme that in humans is encoded by the ''TOP3A'' gene.
Function
This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes t ...
,
* TP53BP1
Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a protein that in humans is encoded by the ''TP53BP1'' gene.
Clinical significance
53BP1 is underexpressed in most cases of triple-negative breast cancer.
...
,[
* WRN,] and
* XRCC2
DNA repair protein XRCC2 is a protein that in humans is encoded by the ''XRCC2'' gene.
Function
This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability a ...
.[
]
References
Further reading
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External links
GeneReviews/NCBI/NIH/UW entry on Bloom Syndrome
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{{DNA repair
DNA replication and repair-deficiency disorders