REPIN1 explained

Replication initiator 1 is a protein that in humans is encoded by the REPIN1 gene.^{[1] [2]} The protein helps enable RNA binding activity as a replication initiation-region protein. The make up of REPIN 1 include three zinc finger hand clusters that organize polydactyl zinc finger proteins containing 15 zinc finger DNA- binding motifs.^[3] It has also been predicted to help in regulation of transcription via RNA polymerase II with it being located in the nucleoplasm. Expression of this protein has been seen in the colon, spleen, kidney, and 23 other tissues within the human body throughout.^[4]

History

REPIN 1 originally was first identified in a study focusing on replication of dihydrofolate reductase gene (dhfr) in Chinese hamsters, with it initiating near stable bent DNA that binds to multiple factors. In the paper scientists used protein DNA cross linking experiments that revealed the 60-kDa polypeptide, with it being labeled by its alternative name RIP60.^[5] Due to the cofractionating of ATP-dependent DNA helicase with DNA-binding activity that was origin specific, the study suggested that RIP60 was involved with chromosomal DNA synthesis in mammalian cells.^[6]

Genetics

REPIN 1 can be found on chromosome 7q36.1 according to the National Center for Biotechnology Information within humans.^[7] REPIN 1 acts as a specific sequence binding protein in human DNA which is required for the start of chromosomal replication. Located in the nucleoplasm and part of the nuclear origin of replication recognition complex within the nucleus, it first binds on 5'-ATT'3' of the sequence. It does this on reiterated sequences downstream of the origin of bidirectional replication (OBR), and at a second 5'-ATT-3' homologous sequence opposite of the orientation within the OBR zone.^[8] It encodes proteins containing fifteen C₂H₂ zinc finger DNA binding motifs to three clusters referred to as hands Z1 (ZFs 1-5), Z2 (ZFs 6-8), and Z3 (ZFs 9-15) with proline rich areas being present between them.^[9]

Function

The function of REPIN 1 is to act as a replication initiator and sequence binding protein for chromosomal replication. Like other zinc finger proteins its physiological functions, molecular mechanisms, and regulations are not fully understood. However due to its high expression in adipose tissue and livers found in sub congenic and congenic rat strains some scientists have seen in as a participant in the regulation of genes. More specifically in those that are involved in lipid droplet formation and fusion, adipogenesis, as well as glucose and fatty acid transport in adipocytes. ^[10] Human in vitro data also suggests REPIN 1's role in adipocyte function and a possible therapeutic target for treating obesity.^[11]

Further reading

• Dailey L, Caddle MS, Heintz N, Heintz NH . Purification of RIP60 and RIP100, mammalian proteins with origin-specific DNA-binding and ATP-dependent DNA helicase activities . Molecular and Cellular Biology . 10 . 12 . 6225–6235 . December 1990 . 2174103 . 362897 . 10.1128/mcb.10.12.6225 .
• Caddle MS, Dailey L, Heintz NH . RIP60, a mammalian origin-binding protein, enhances DNA bending near the dihydrofolate reductase origin of replication . Molecular and Cellular Biology . 10 . 12 . 6236–6243 . December 1990 . 2247056 . 362898 . 10.1128/mcb.10.12.6236 .
• Mastrangelo IA, Held PG, Dailey L, Wall JS, Hough PV, Heintz N, Heintz NH . RIP60 dimers and multiples of dimers assemble link structures at an origin of bidirectional replication in the dihydrofolate reductase amplicon of Chinese hamster ovary cells . Journal of Molecular Biology . 232 . 3 . 766–778 . August 1993 . 8355269 . 10.1006/jmbi.1993.1430 .
• Montigny WJ, Houchens CR, Illenye S, Gilbert J, Coonrod E, Chang YC, Heintz NH . Condensation by DNA looping facilitates transfer of large DNA molecules into mammalian cells . Nucleic Acids Research . 29 . 9 . 1982–1988 . May 2001 . 11328883 . 37261 . 10.1093/nar/29.9.1982 .
• Brandenberger R, Wei H, Zhang S, Lei S, Murage J, Fisk GJ, Li Y, Xu C, Fang R, Guegler K, Rao MS, Mandalam R, Lebkowski J, Stanton LW . 6 . Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation . Nature Biotechnology . 22 . 6 . 707–716 . June 2004 . 15146197 . 10.1038/nbt971 . 27764390 .
• Kim MY, Jeong BC, Lee JH, Kee HJ, Kook H, Kim NS, Kim YH, Kim JK, Ahn KY, Kim KK . 6 . A repressor complex, AP4 transcription factor and geminin, negatively regulates expression of target genes in nonneuronal cells . Proceedings of the National Academy of Sciences of the United States of America . 103 . 35 . 13074–13079 . August 2006 . 16924111 . 1551900 . 10.1073/pnas.0601915103 . free . 2006PNAS..10313074K .

Notes and References

1. Houchens CR, Montigny W, Zeltser L, Dailey L, Gilbert JM, Heintz NH . The dhfr oribeta-binding protein RIP60 contains 15 zinc fingers: DNA binding and looping by the central three fingers and an associated proline-rich region . Nucleic Acids Research . 28 . 2 . 570–581 . January 2000 . 10606657 . 102514 . 10.1093/nar/28.2.570 .
2. Web site: Entrez Gene: REPIN1 replication initiator 1.
3. Heiker JT, Klöting N . Replication initiator 1 in adipose tissue function and human obesity . Vitamins and Hormones . 91 . 97–105 . 2013-01-01 . 23374714 . Academic Press . 10.1016/B978-0-12-407766-9.00005-5 . 9780124077669 . Litwack G .
4. Web site: REPIN1 replication initiator 1 [Homo sapiens (human)] - Gene - NCBI ]. 2023-10-18 . www.ncbi.nlm.nih.gov.
5. Krüger J, Berger C, Weidle K, Schleinitz D, Tönjes A, Stumvoll M, Blüher M, Kovacs P, Klöting N . 6 . Metabolic effects of genetic variation in the human REPIN1 gene . International Journal of Obesity . 43 . 4 . 821–831 . April 2019 . 29915365 . 10.1038/s41366-018-0123-0 . 49297306 .
6. Dailey L, Caddle MS, Heintz N, Heintz NH . Purification of RIP60 and RIP100, mammalian proteins with origin-specific DNA-binding and ATP-dependent DNA helicase activities . Molecular and Cellular Biology . 10 . 12 . 6225–6235 . December 1990 . 2174103 . 362897 . 10.1128/mcb.10.12.6225-6235.1990 .
7. Web site: REPIN1 replication initiator 1 [Homo sapiens (human)] - Gene - NCBI ]. 2023-10-18 . www.ncbi.nlm.nih.gov.
8. Web site: UniProt . 2023-10-18 . www.uniprot.org.
9. Klöting N, Wilke B, Klöting I . Triplet repeat in the Repin1 3'-untranslated region on rat chromosome 4 correlates with facets of the metabolic syndrome . Diabetes/Metabolism Research and Reviews . 23 . 5 . 406–410 . July 2007 . 17173329 . 10.1002/dmrr.713 . 84633542 .
10. Ruschke K, Illes M, Kern M, Klöting I, Fasshauer M, Schön MR, Kosacka J, Fitzl G, Kovacs P, Stumvoll M, Blüher M, Klöting N . 6 . Repin1 maybe involved in the regulation of cell size and glucose transport in adipocytes . en-US . Biochemical and Biophysical Research Communications . 400 . 2 . 246–251 . September 2010 . 20727851 . 10.1016/j.bbrc.2010.08.049 .
11. Heiker JT, Klöting N . Replication initiator 1 in adipose tissue function and human obesity . Vitamins and Hormones . 91 . 97–105 . January 2013 . 23374714 . 10.1016/B978-0-12-407766-9.00005-5 . Academic Press . 9780124077669 . Litwack G .