Page 1 \ ?^p 6r.1 CELL CYCLE CONTROL OF HUMAN H4 ...

Aziz f: Celi Ctcle Cotutol ol H4 Aene na&iblon
produclion of hisrone prot6ins duing S-phase and it has b8en knownlormore
|han rwo decad€s thal hislone symhesis ia coudod wirh the replicative phase
o' the csllcycl€ (Bobblns and Borun, 1967). Lal€r slldl6s hav6 also shown
that histone p.orein synrhesis is directly coupled wilh ONA synlhesis in lhe S-
phase ot rhe celr cycre wirh advgnc€d r€chniqu€s ol mol6cular bioloqy. These
srldies have r€vealed a complicated m€cha.ism ol cell cycr6 regulalon in
which rh€ le@l ol histone mRNAs is r69ul6ted by both iranscnpl'onal aod
posl-transcriptional contfo (see Fig. ?). Two vpes ot svalegi€s hav€ been
used ro srudy hisron€ mRNA meraborism during th€ cell cycle. The firsl
stralegy nvolved synchronlzed c€ll cuitlr€s whi6h wer€ used lo obsotu€ lhe
acclnualon ol hlstone mRNA in the cellcycle withod any interrudion The
second appoach involved rhe interrudion ol lh€ cell cyc.ls wilh inhibirors oi
DNA chan elongalion, lo observe if oNA synthosls is af impodant event for
conlinuols production ot hlstone mFNA. Ths majorresulls s::cwthallhe DNA
replication is important lor rhe synthesis ol hisrone mRNA In mo$ ot the
eukaryoric cerrs, hgh lever accLrmulaio. ol hi$on6 mFNA G obsotued dun.g
rhe s phase. ThB level ot histon6 oFNA elevabs 15 - 30 ,old as cells pass
rhrough rhe G1 ro s-phase and p€ak l€v€rs are obseryed i. th€ middle oi s-
phase (3 ' 6) ho!.s at1e. rhe ell released lrom block (Ehinger €t al., 1990;
Marzrull and Grave, 198.1 Srein et aL, 1984r Heintz e! al., 1983i Baumbach et
ar., 1987iPlumb era/., 19S3; Mor s era/., 1991; Hads era/., 1991i Anishevsky
er a/., 19a4). When DNA sydhesis is disiurbed, histong mRNAs disappear
lrom the cyroplasm rapid y (Wu and Bonn€r, 1981j H6i.lz €tal., 1983i oeL sie
er a/.. 1983i Snhan er a/., 1983). The higher eukaryoles