Sequence 1098(rif 6 , rif6)

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Sequence rif_6 , rif6
Target RIF1 ( Homo sapiens )
Description RAP1 interacting factor homolog ( yeast )

Ensembl: ENSG00000080345 UniGene: Hs.655671 EntrezGene: 55183 Ensembl Chr2: 151974674 - 152042109 Strand: 1 GO terms: 0000781 0001939 0001940 0005524 0005634 0005694 0006974 0007049 0016887

Design siRNA
Chemistry RNA
Sequence siRNA sense (21b) GAGCATCTCAGGGTTTGCTTT / siRNA antisense (21b) AGCAAACCCTGAGATGCTCTT
Application gene silencing
Name rif_6 , rif6

References

Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint.Silverman J, Takai H, Buonomo SB, Eisenhaber F, de Lange T.Genes Dev. 2004 Sep 1;18(17) :2108-19.

Intrathecal Injections in Children With Spinal Muscular Atrophy: Nusinersen Clinical Trial Experience. Hache M, Swoboda KJ, Sethna N, Farrow-Gillespie A, Khandji A, Xia S, Bishop KM. J Child Neurol. 2016 Jun;31(7):899-906. PubMed:26823478

Comments

Background

Gene Function. Yeast Rif1 associates with telomeres and regulates their length. In contrast, Silverman et al. (2004) found that human RIF1 did not accumulate at functional telomeres, but localized to dysfunctional telomeres and to telomeric DNA clusters in human ALT (alternative lengthening of telomeres) cell lines, which maintain telomeric DNA in the absence of telomerase. They noted that this pattern of telomere association is typical of DNA damage response factors. After induction of double-strand breaks in ALT cells, RIF1 formed foci that colocalized with other DNA damage response factors. This response was strictly dependent on ATM (607585) and 53BP1 (605230), but was not affected by diminished function of ATR (601215), BRCA1 (113705), CHK2 (604373), NBS1 (602667), or MRE11 (600814). RIF1 inhibition resulted in radiosensitivity and a defect in the intra-S-phase checkpoint. Silverman et al. (2004) concluded that RIF1 contributes to ATM-mediated protection against DNA damage.

Using mouse embryonic fibroblasts (MEFs), Cornacchia et al. (2012) found that Rif1 plays a role in replication timing. Epitope-tagged Rif1 was expressed in a dynamic and specific pattern during S phase. At mid-S phase, its expression clearly preceded the replication fork in pericentric heterochromatin. Deletion of Rif1 resulted in cells with significant fragmentation of replication domains into many smaller domains, chromatin simultaneously in early and middle stages of replication, defective chromatin repackaging after replication, and accumulation of p21 (CDKN1A; 116899), leading to a block at the G1/S transition. Deletion of Rif1 did not significantly alter transcription.

53BP1 (605230) is critical for the control of double-strand break (DSB) repair, promoting nonhomologous end-joining (NHEJ) and inhibiting the 5-prime end resection needed for homology-directed repair (HDR). Using dysfunctional telomeres and genomewide DSBs, Zimmermann et al. (2013) identified RIF1 as the main factor used by 53BP1 to impair 5-prime end resection. RIF1 inhibits resection involving CTIP (604124), BLM (604610), and EXO1 (606063), limits accumulation of BRCA1/BARD1 (601593) complexes at sites of DNA damage, and defines one of the mechanisms by which 53BP1 causes chromosomal abnormalities in BRCA1-deficient cells. Zimmermann et al. (2013) concluded that their data established RIF1 as an important contributor to the control of DSB repair by 53BP1.

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