“Exonuclease 1”的意思、由来-开放百科全书

This gene encodes a protein with 5' to 3' exonuclease activity as well as an RNase H activity (endonuclease activity cleaving RNA on DNA/RNA hybrid).^[4] It is similar to the Saccharomyces cerevisiae protein Exo1 which interacts with Msh2 and which is involved in DNA mismatch repair and homologous recombination. Alternative splicing of this gene results in three transcript variants encoding two different isoforms.^[3]

Meiosis

ExoI is essential for meiotic progression through metaphase I in the budding yeast Saccharomyces cerevisiae and in mouse.^[5]^[6]

Recombination during meiosis is often initiated by a DNA double-strand break (DSB) as illustrated in the accompanying diagram. 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 "invades" the DNA of a homologous chromosome that is not broken, forming a displacement loop (D-loop). 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 Homologous recombination). The pathway leading to a CO involves a double Holliday junction (DHJ) intermediate. Holliday junctions need to be resolved for CO recombination to be completed.

During meiosis in S. cerevisiae, transcription of the Exo1 gene is highly induced.^[5] In meiotic cells, Exo1 mutation reduces the processing of DSBs and the frequency of COs.^[5] Exo1 has two temporally and biochemically distinct functions in meiotic recombination.^[7] First, Exo1 acts as a 5’–3’ nuclease to resect DSB-ends. Later in the recombination process, Exo1 acts to facilitate the resolution of DHJs into COs, independently of its nuclease activities. In resolving DHJs, Exo 1 acts together with MLH1-MLH3 heterodimer (MutL gamma) and Sgs1 (ortholog of Bloom syndrome helicase) to define a joint molecule resolution pathway that produces the majority of crossovers.^[8]

Male mice deficient for Exo1 are capable of normal progress through the pachynema stage of meiosis, but most germ cells fail to progress normally to metaphase I due to dynamic loss of chiasmata .^[6]

Interactions

References

1. ^{{cite journal | vauthors = ((Wilson DM III)), Carney JP, Coleman MA, Adamson AW, Christensen M, Lamerdin JE | title = Hex1: a new human Rad2 nuclease family member with homology to yeast exonuclease 1 | journal = Nucleic Acids Res | volume = 26 | issue = 16 | pages = 3762–8 |date=September 1998 | pmid = 9685493 | pmc = 147753 | doi =10.1093/nar/26.16.3762 }}
2. ^¹{{cite journal | vauthors = Schmutte C, Marinescu RC, Sadoff MM, Guerrette S, Overhauser J, Fishel R | title = Human exonuclease I interacts with the mismatch repair protein hMSH2 | journal = Cancer Res | volume = 58 | issue = 20 | pages = 4537–42 |date=November 1998 | pmid = 9788596 | pmc = | doi = }}
3. ^¹{{Cite web| title = Entrez Gene: EXO1 exonuclease 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9156| accessdate = }}
4. ^{{cite journal | journal = J. Biol. Chem. | vauthors = Qiu J, Qian Y, Chen V, Guan MX, Shen B | title = Human exonuclease 1 functionally complements its yeast homologues in DNA recombination, RNA primer removal, and mutation avoidance. |date=June 1999 | pmid = 10364235 | doi = 10.1074/jbc.274.25.17893 | volume = 274 | issue = 25 | pages = 17893–900}}
5. ^¹²{{vcite2 journal |vauthors=Tsubouchi H, Ogawa H |title=Exo1 roles for repair of DNA double-strand breaks and meiotic crossing over in Saccharomyces cerevisiae |journal=Mol. Biol. Cell |volume=11 |issue=7 |pages=2221–33 |year=2000 |pmid=10888664 |pmc=14915 |doi= 10.1091/mbc.11.7.2221|url=}}
6. ^¹{{vcite2 journal |vauthors=Wei K, Clark AB, Wong E, Kane MF, Mazur DJ, Parris T, Kolas NK, Russell R, Hou H, Kneitz B, Yang G, Kunkel TA, Kolodner RD, Cohen PE, Edelmann W |title=Inactivation of Exonuclease 1 in mice results in DNA mismatch repair defects, increased cancer susceptibility, and male and female sterility |journal=Genes Dev. |volume=17 |issue=5 |pages=603–14 |year=2003 |pmid=12629043 |pmc=196005 |doi=10.1101/gad.1060603 |url=}}
7. ^{{vcite2 journal |vauthors=Zakharyevich K, Ma Y, Tang S, Hwang PY, Boiteux S, Hunter N |title=Temporally and biochemically distinct activities of Exo1 during meiosis: double-strand break resection and resolution of double Holliday junctions |journal=Mol. Cell |volume=40 |issue=6 |pages=1001–15 |year=2010 |pmid=21172664 |pmc=3061447 |doi=10.1016/j.molcel.2010.11.032 |url=}}
8. ^{{vcite2 journal |vauthors=Zakharyevich K, Tang S, Ma Y, Hunter N |title=Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvase |journal=Cell |volume=149 |issue=2 |pages=334–47 |year=2012 |pmid=22500800 |pmc=3377385 |doi=10.1016/j.cell.2012.03.023 |url=}}
9. ^{{cite journal |last=Rasmussen |first=L J |author2=Rasmussen M|author3=Lee B|author4=Rasmussen A K|author5=Wilson D M|author6=Nielsen F C|author7=Bisgaard H C |date=June 2000 |title=Identification of factors interacting with hMSH2 in the fetal liver utilizing the yeast two-hybrid system. In vivo interaction through the C-terminal domains of hEXO1 and hMSH2 and comparative expression analysis |journal=Mutat. Res. |volume=460 |issue=1 |pages=41–52 | issn = 0027-5107| pmid = 10856833 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = | doi=10.1016/S0921-8777(00)00012-4|citeseerx=10.1.1.614.1507 }}
10. ^¹{{cite journal |last=Schmutte |first=C |author2=Sadoff M M|author3=Shim K S|author4=Acharya S|author5=Fishel R |date=August 2001 |title=The interaction of DNA mismatch repair proteins with human exonuclease I |journal=J. Biol. Chem. |volume=276 |issue=35 |pages=33011–8 | issn = 0021-9258| pmid = 11427529 |doi = 10.1074/jbc.M102670200 | bibcode = | oclc =| id = | url = | language = | format = | accessdate = | laysummary = | laysource = | laydate = | quote = }}

Meiosis

Interactions

References

Further reading