Article Figures & Data
Figures
- Fig. 1.
MicroRNAs implicated in the generation of CIN. miR-22 directly regulates MDC1 through HR-mediated DNA repair and contributes to CIN. miR-26a, miR-28 and miR-186 regulates genes involved in cell cycle checkpoints and contributes to centrosome defect, aneuploidy, double minute, dicentric, and ring chromosomes rendering CIN.
Tables
Name Target Mechanism Correlation to CIN References TERRA Terc
TERT
Ku70/80
TRF1/2
TelomereTranscribed from telomeres; regulate telomere length via inhibition of telomerase (Terc, TERT), exonuclease degradation of chromosome ends (Ku70/80-exonuclease 1), formation of telomeric heterochromatin (TRF2-ORC1) and protection of chromosome ends from DNA damage (DNA:RNA hybrids) Negative/positive Schoeftner and Blasco (2008), Deng et al. (2009), Redon et al. (2010), Aguilera and García-Muse (2012), Pfeiffer and Lingner (2012), Sagie et al. (2017), Mei et al. (2021) cenRNA CENP-A
HJURP
CENP-C
INCENP
Aurora BTranscribed from centrosomal DNA; Assists kinetochore assembly via interaction with various centromere-associated proteins and the chromosome passenger complex Positive Murata-Hori and Wang (2002), Wong et al. (2007), Portella et al. (2011), Kato et al. (2013), Ideue et al. (2014), Quénet and Dalal (2014), McNulty et al. (2017) Enhancer RNAs AID In B cells, AID off-targeting to regions other than the immunoglobulin loci has been related to convergent transcription of enhancer RNAs. Convergent transcription leads to formation of R loops, which impose genomic fragility if not resolved by the RNA exosome, leading to translocations between proto-oncogenes and the potent immunoglobulin enhancers. Positive Meng et al. (2014), Qian et al. (2014), Pefanis et al. (2015) PCAT2 CENP-A, HIRA, DAXX Transcribed from fragile 8q24 locus; causes local, ectopic recruitment of CENP-A and other centromere-associated proteins resulting in genome fragility Positive Arunkumar et al. (2022) Ginir and Giniras Cep112
Brca1Disruption of the Cep112-Brca1 interaction and downregulation of Cep112 and Brca1 causes centromere defects, chromosome missegregation and increased occurrence of DNA double strand breaks. Positive Panda et al. (2018) GUARDIN miR-23a
BRCA1-BARD1Maintains TFR2 (shelterin complex component) expression via sponging of miR-23a to prevent telomere dysfunction.
Acts as an RNA scaffold for BRCA1-BARD1, forming a ribonucleoprotein complex that influences double strand break repair.Negative Hu et al. (2018) CCAT2 BOP1
AURKBPositively regulates BOP1 expression which in turn upregulates phosphorylation and activation of AURKB. Possibly mediates BOP1-AURKB interaction by scaffolding. Increased pAURKB disrupts chromosome-microtubule attachments and chromosome missegregation. Positive Ling et al. (2013), Chen et al. (2020) NORAD PUMILIO (PUM1/PUM2)
SAM68Mediates phase-separation of PUM1 and PUM2 proteins, which bind to NORAD via PUMILIO response elements and/or via SAM68. This in turn inhibits the repressive effect of PUMILIO proteins on mRNA targets involved in DNA damage repair and mitosis regulation. Negative Lee et al. (2016), Tichon et al. (2018), Elguindy and Mendell (2021) BARD1, BRCA1-associated RING domain 1; DAXX, death domain–associated protein; HIRA, histone cell cycle regulator; HJURP, Holliday junction recognition protein; INCENP, inner centromere protein; ORC1, origin recognition complex subunit 1; PUM1/PUM2, PUMILIO homolog 1/PUMILIO homolog 2; TERT, telomerase reverse transcriptase.
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