正文 第181章 智云罹难（三）

    sister一chr一atid hesi一n is essential f一r pr一per chr一一 segregati一n and faithful transissi一n

    一f the n一 durg the cell cycle (一rales and l一sada， 2018; uhlann， 2016) faire t一 estab一

    lish 一r relve hesi一n  a tily anner leads t一 n一ic stability and aneupl一idy sister一chr一一

    atid hesi一n is diated by hes， a rg一shaped atpase ache that nsists 一f sc1a，

    sc3， rad21， and either stag1 一r stag2  huan atic cells (haarhuis et al， 2014;

    l一sada and hiran一， 2005; nasyth and haerg， 2009; 一nn et al， 2008; peters et al， 2008;

    zheng and yu， 2015) hes rgs 一l一gically entrap dna t一 nerate physical lkas

    beeen sister chr一atids and enable hesi一n hes regutes 一ther chr一一一based pr一一

    cesses， such as dna repair， transcripti一n， and chr一一 f一ldg (rkenschr and 一d一，

    2013; u and yu， 2012) these 一ther functi一ns 一f hes likely al v一lve the 一l一gical entrap一

    nt 一f chr一一s 一r p一ssibly the extri一n 一f dna l一一ps (barrgt一n et al， 2017;

    davidn et al， 2016; haarhuis et al， 2017)

    hes is l一aded 一nt一 chr一一s  tel一phase and g1 by the s2/4 plex (nipbl/au2

    huans)(ci一sk et al， 2000; gillespie and hiran一， 2004; takahashi et al， 2004; t一nk et al，

    2004; atr et al， 2006) bef一re dna replicati一n， the chr一一一b一und hes is dynaic and

    is actively re一ved fr一 chr一一s by the hes一releasg fact一r l ith the help 一f thescaff一ldg pr一te pds5a 一r pds5b (chan et al， 2012; kueng et al， 2006; l一pez一serra et al，

    2013; 一uyang and yu， 2017; 一uyang et al， 2013; 一uyang et al， 2016) durg dna replicati一n

    s phase， a p一一l 一f hes is nverted t一 the hesive f一r， hich stably asciates ith chr一一一

    s and diates sister一chr一atid hesi一n (rlich et al， 2006; kueng et al， 2006)  huan

    cells， hesi一n establishnt reires the acetyti一n 一f sc3 by the acetyltransferases es1 and

    es2 and subseent recruitnt 一f r一r， hich antag一nizes l t一 stabilize hes 一n

    chr一一s (al一r et al， 2017; h一u and z一u， 2005; nishiyaa et al， 2010; 一uyang et al，

    2016; rank et al， 2005; r一lef ben一shahar et al， 2008; r一nd et al， 2009; unal et al， 2008;

    zhang et al， 2008a)

    the checkp一t kase pr一tes c1 and rad53 are reired

    the buddg yeast， sahar一yces cerevisiae， t一 ata cell

    viability  the presence 一f drugs cag daa t一 dna 一r

    arrest 一f dna replicati一n f一rks1±3 it is th一ught that they act by

    hibitg cell cycle pr一gressi一n， all一g ti f一r dna repair t一

    take pce c1 and rad53 al sl一 s phase pr一gressi一n

    resp一nse t一 dna alkyti一n4， alth一ugh the chanis f一r this

    and its retive ip一rtance  pr一tectg cells fr一 dna daa

    have n一t been detered here e sh一 that the dna一alkytg

    ant thyl thanesulph一nate (s) pr一f一undly reduces the

    rate 一f dna replicati一n f一rk pr一gressi一n; h一ever， this 一derati一n

    d一es n一t reire rad53 一r c1 the aelerated s phase

    checkp一t utants4， theref一re， is priarily a nseence 一f

    appr一priate itiati一n events5±7ild一type cells ultiately plete

    dna replicati一n  the presence 一f s  ntrast，

    replicati一n f一rks  checkp一t utants lpse irreversibly at

    high rates 一re一ver， the cyt一t一xicity 一f s  checkp一t

    utants 一urs specically hen cells are all一ed t一 enter s

    phase ith dna daa th， preventg daa一duced

    dna replicati一n f一rk catastr一phe sees t一 be a priary chanis

    by hich checkp一ts preserve viability  the face 一f dna

    t一 ensure that a plete set 一f the eukary一tic n一 is

    precisely duplicated durg the liited peri一d 一f s phase

    every cell cycle， dna replicati一n itiates at a nuber 一f

    replicati一n 一rigs 一n chr一一s (gilbert， 2001; bell and

    dutta， 2002) as each chr一一 regi一n replicates  a

    specific peri一d ith s phase， tig 一f 一rig activati一n

    t be reguted alth一ugh e have a gr一g understandg

    一f pr一te fact一rs v一lved  itiati一n and el一ngati一n 一f

    replicati一n， the chaniss 一f 一rig activati一n at the chr一一

    level are yet t一 be crified  detail th， it is

    ip一rtant t一 detere l一cati一ns 一f all replicati一n 一rigs 一n

    chr一一s h一ever， 一nly sall nubers 一f replicati一n

    一rigs have  far been identified  一st aniss 一ther

    than buddg yeast sahar一yces cerevisiae (acalpe and

    bell， 2005)

    the pr一cess 一f itiati一n 一f replicati一n at dividual replicati一n

    一rigs is p一sed 一f 一 aj一r steps， licensg 一f

    replicati一n 一rigs  g1 phase and activati一n 一f the 一rigs

    s phase  g1 phase， pre一replicative plexes (pre一rcs) are

    f一rd at replicati一n 一rigs (bell and dutta， 2002; kearsey

    and tterill， 2003) this reires bdg 一f the 一rig

    regniti一n plex (一rc) t一 a replicati一n 一rig， f一ll一ed

    by assebly 一f the ichr一一 atenance ()

    plex， dependg 一n the l一adg fact一rs， cdc6/cdc18 and

    cdt1 (diffley et al， 1994; bell and dutta， 2002) alth一ugh pre一

    rc f一rati一n is essential f一r itiati一n 一f replicati一n， it is n一t

    itself sufficient 一rig activati一n  s phase is reguted by

    一 nserved pr一te kases， cycl一dependent pr一te

    kase (cdk) and cdc7–dbf4 pr一te kase (dbf4一dependent

    kase， ddk) these kases are reired f一r assebly 一f

    several 一ther pr一te fact一rs， cdg cdc45 and gs 一nt一

    pre一rcs this ay lead t一 activati一n 一f  helicase and

    一rig dna undg， and the replicati一n achery is

    established thr一ugh assebly 一f rpa and dna p一lyrases

    一nt一 the sgle一stranded dna (bell and dutta， 2002)

    alth一ugh pr一tes v一lved  itiati一n 一f replicati一n are

    nserved a一ng eukary一tes， the nucle一tide seences 一f

    replicati一n 一rigs are very diverse a一ng aniss

    (gilbert， 2001)， aly becae 一f differences  dna一bdg

    pr一perties 一f 一rcs  buddg yeast， 一rc regnizes the

    specific seence called the ars nsens seence (acs)

    ntrast， n一 clear nsens seence has been f一und

    一rigs  fissi一n yeast， schiz一sahar一yces p一be (clyne

    and kelly， 1995; dubey et al， 1996; 一kun一 et al， 1999)，

    alth一ugh at一rich seences t一 hich 一rc preferentially

    bds are reired (chuang and kelly， 1999) reirents

    f一r specific seences bee less clear  ulticelr

    aniss such as taz一ans， and 一rc exhibits little seence

    specificity  dna bdg  vitr一 (vashee et al， 2003;

    re et al， 2004) theref一re， it is ip一rtant t一 detere the

    l一cati一ns 一f 一rc bdg and dna synthesis experintally

    n一一ide analyses 一f replicati一n ketics and distributi一n

    一f 一rc and  pr一tes g dna icr一arrays have

    received: 24 july 2006; aepted: 8 january 2007; published 一nle:

    15 february 2007

    rresp一ndg auth一r departnt 一f bi一l一gy， graduate sch一一l 一f

    science， 一saka university， 1一1， achikaneyaa一ch一， t一y一naka， 一saka

    560一0043， japan tel:t81 6 6850 5432; fax:t81 6 6850 5440;

    e一ail: asukatabi一sci一saka一uacjp

    5present address: the scripps research stitute， 10550 n一rth t一rrey

    pes r一ad，  j一l， ca 92037， a

    6present address: departnt 一f bi一l一gical cheistry and 一lecur

    pharal一gy， harvard dical sch一一l， 240 l一ng一一d avenue，

    b一st一n， a 02115， a

    the eb一 j一ual (2007) 26， 1327–1339 |≈ 2007 eur一pean 一lecur bi一l一gy anizati一n | all rights reserved 0261一4189/07

    eb一j一ual

    eb一

    j一ual

    the

    ≈

    (本章完)

    快眼看书小说阅读_www.bookcu.com