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Bloom syndrome protein

From Wikipedia, the free encyclopedia

BLM
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesBLM, BS, RECQ2, RECQL2, RECQL3, Bloom syndrome RecQ like helicase, BLM RecQ like helicase, MGRISCE1
External IDsOMIM: 604610 MGI: 1328362 HomoloGene: 47902 GeneCards: BLM
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000057
NM_001287246
NM_001287247
NM_001287248

NM_001042527
NM_007550

RefSeq (protein)

NP_000048
NP_001274175
NP_001274176
NP_001274177
NP_001274177.1

NP_001035992
NP_031576

Location (UCSC)Chr 15: 90.72 – 90.82 MbChr 7: 80.1 – 80.18 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is not expressed in Bloom syndrome.[5]

The Bloom syndrome gene product is related to the RecQ subset of DExH box-containing DNA helicases and has both DNA-stimulated ATPase and ATP-dependent DNA helicase activities. Mutations causing Bloom syndrome delete or alter helicase motifs and may disable the 3' → 5' helicase activity. The normal protein may act to suppress inappropriate homologous recombination.[6]

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Transcription

Meiosis

A current model of meiotic recombination, initiated by a double-strand break or gap, followed by pairing with an homologous chromosome and strand invasion to initiate the recombinational repair process. Repair of the gap can lead to crossover (CO) or non-crossover (NCO) of the flanking regions. CO recombination is thought to occur by the Double Holliday Junction (DHJ) model, illustrated on the right, above. NCO recombinants are thought to occur primarily by the Synthesis Dependent Strand Annealing (SDSA) model, illustrated on the left, above. Most recombination events appear to be the SDSA type.

Recombination during meiosis 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 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 encodes an ortholog of the Bloom syndrome (BLM) protein that is designated Sgs1 (Small growth suppressor 1). Sgs1(BLM) is a helicase that functions in homologous recombinational repair of DSBs. The Sgs1(BLM) helicase appears to be a central regulator of most of the recombination events that occur during S. cerevisiae meiosis.[7] 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.[7]

In the plant Arabidopsis thaliana, homologs of the Sgs1(BLM) helicase act as major barriers to meiotic CO formation.[8] 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.[9] Sequela-Arnaud et al.[8] 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.

DNA repair and apoptosis

Bloom syndrome protein facilitates DNA repair when cells are stressed by agents that cause DNA damages, specifically when DNA replication forks are stalled. Damage present during S phase of the cell cycle causes Bloom syndrome protein to rapidly form foci with gamma H2AX protein at replication forks that develop DNA breaks.[10] These BLM foci then recruit repair complexes composed of BRCA1 and NBS1 proteins to the stalled replication forks. In addition to its role in repairing DNA damages, Bloom syndrome protein facilitates apoptosis (programmed cell death), a process dependent on p53 protein when cells are stressed by agents that cause unrepairable DNA damage, particularly damage that causes stalled DNA replication forks.[10][11]

Both Repair of DNA damages and apoptosis are enzymatic processes necessary for maintaining genome integrity in humans. Cells that are deficient in DNA repair tend to accumulate DNA damages, and when such cells are also defective in apoptosis they tend to survive even though excessive DNA damage is present.[12] Replication of DNA in such cells tends to lead to mutations and such mutations may cause cancer. Thus Bloom syndrome protein appears to have two roles related to the prevention of cancer, where the first role is to promote repair of a specific class of damages and the second role is to induce apoptosis if the level of such DNA damage is beyond the cell’s repair capability[12]

Interactions

Bloom syndrome protein has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000197299 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030528 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  19. ^ Shastri, Vivek; Subramanian, Veena (7 September 2021). "A novel cell-cycle-regulated interaction of the Bloom syndrome helicase BLM with Mcm6 controls replication-linked processes". Nucleic Acids Research. 49 (15): 8699–8713. doi:10.1093/nar/gkab663. PMC 8421143. PMID 34370039.
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Further reading

External links

This page was last edited on 25 March 2024, at 08:31
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