穿越之盛世隐殇

    cohesin is loaded onto chromosomes in telophase and g1 by the scc2/4 plexbefore dna replication， the chromosome-bound cohesin is dynamic and

    is actively removed from chromosomes by the cohesin-releasing factor l with the help of thescaffolding protein pds5a or pds5bduring dna replication

    in s phase， a pool of cohesin is converted to the cohesive form， which stably associates with chromo-

    somes and mediates sister-chromatid cohesionin human

    cells， cohesion establishment requires the acetylation of smc3 by the acetyltransferases esco1 and

    esco2 and subsequent recruitment of sororin， which antagonizes l to stabilize cohesin on

    chromosomes

    the checkpoint kinase proteins mec1 and rad53 are required in

    the budding yeast， haromyces cerevisiae， to maintain cell

    viability in the presence of drugs causing damage to dna or

    arrest of dna replication forks1±3 it is thought that they act by

    inhibiting cell cycle progression， allowing time for dna repair to

    take place mec1 and rad53 also slow s phase progression in

    response to dna alkylation4， although the mechanism for this

    and its relative importance in protecting cells from dna damage

    have not been determined here we show that the dna-alkylating

    agent methyl methanesulphonateprofoundly reduces the

    rate of dna replication fork progression; however， this moderation

    does not require rad53 or mec1 the accelerated s phase in

    checkpoint mutants4， therefore， is primarily a consequence of

    inappropriate initiation events5±7wild-type cells ultimately plete

    dna replication in the presence of mms in contrast，

    replication forks in checkpoint mutants collapse irreversibly at

    high rates moreover， the cytotoxicity of mms in checkpoint

    mutants occurs specically when cells are allowed to enter s

    phase with dna damage thus， preventing damage-induced

    dna replication fork catastrophe seems to be a primary mechanism

    by which checkpoints preserve viability in the face of dna

    to ensure that a plete set of the eukaryotic genome is

    precisely duplicated during the limited period of s phase in

    every cell cycle， dna replication initiates at a number of

    replication origins on chromosomesas each chromosome region replicates in a

    specific period within s phase， timing of origin activation

    must be regulated although we have a growing understanding

    of protein factors involved in initiation and elongation of

    replication， the mechanisms of origin activation at the chromosome

    level are yet to be clarified in detail thus， it is

    important to determine locations of all replication origins on

    chromosomes however， only small numbers of replication

    origins have so far been identified in most anisms other

    than budding yeast haromyces cerevisiae

    the process of initiation of replication at individual replication

    origins is posed of two major steps， licensing of

    re




第181章 智云罹难（三）
    sister-chromatid cohesion is essential for proper chromosome segregation and faithful transmission

    of the genome during the cell cyclefailure to estab-

    lish or resolve cohesion in a timely manner leads to genomic instability and aneuploidy sister-chro-

    matid cohesion is mediated by cohesin， a ring-shaped atpase machine that consists of smc1a，

    smc3， rad21， and either stag1 or stag2 in human somatic cellscohesin rings topologically entrap dna to generate physical linkages

    between sister chromatids and enable cohesion cohesin regulates other chromosome-based pro-

    cesses， such as dna repair， transcription， and chromosome foldingthese other functions of cohesin likely also involve the topological entrap-

    ment of chromosomes or possibly the extrusion of dna loops

    cohesin is loaded onto chromosomes in telophase and g1 by the scc2/4 plexbefore dna replication， the chromosome-bound cohesin is dynamic and

    is actively removed from chromosomes by the cohesin-releasing factor l with the help of thescaffolding protein pds5a or pds5bduring dna replication

    in s phase， a pool of cohesin is converted to the cohesive form， which stably associates with chromo-

    somes and mediates sister-chromatid cohesionin human

    cells， cohesion establishment requires the acetylation of smc3 by the acetyltransferases esco1 and

    esco2 and subsequent recruitment of sororin， which antagonizes l to stabilize cohesin on

    chromosomes

    the checkpoint kinase proteins mec1 and rad53 are required in

    the budding yeast， haromyces cerevisiae， to maintain cell

    viability in the presence of drugs causing damage to dna or

    arrest of dna replication forks1±3 it is thought that they act by

    inhibiting cell cycle progression， allowing time for dna repair to

    take place mec1 and rad53 also slow s phase progression in

    response to dna alkylation4， although the mechanism for this

    and its relative importance in protecting cells from dna damage

    have not been determined here we show that the dna-alkylating

    agent methyl methanesulphonateprofoundly reduces the

    rate of dna replication fork progression; however， this moderation

    does not require rad53 or mec1 the accelerated s phase in

    checkpoint mutants4， therefore， is primarily a consequence of

    inappropriate initiation events5±7wild-type cells ultimately plete

    dna replication in the presence of mms in contrast，

    replication forks in checkpoint mutants collapse irreversibly at

    high rates moreover， the cytotoxicity of mms in checkpoint

    mutants occurs specically when cells are allowed to enter s

    phase with dna damage thus， preventing damage-induced

    dna replication fork catastrophe seems to be a primary mechanism

    by which checkpoints preserve viability in the face of dna

    to ensure that a plete set of the eukaryotic genome is

    precisely duplicated during the limited period of s phase in

    every cell cycle， dna replication initiates at a number of

    replication origins on chromosomesas each chromosome region replicates in a