Asterisk, quantitation of JH dosage was performed only on bands amplied above the RS control level.Top, diamidinophenylindole staining; bottom, SKY analysis.In total, contained at least one anomaly.We conclude that XRCC and, by extension, NHEJ is crucial for maintaining mammalian genomic stability.However, embryonic lethality, increased <a href="https://www.ncbi.nlm.nih.gov/pubmed/1278093"></a>
neuronal apoptosis and cellular proliferation defects of XRCC mice appear to result from a pdependent response to DNA damage that has not been repaired, as opposed to defective NHEJ per se.We conclude that the NHEJ requirements for lymphogenesis are more stringent than for neurogenesis, as development of a largely functional nervous system can occur in the absence of XRCC.Genomic probes for FISH analysis were nicktranslated using biotindUTP or digoxigenindUTP by standard procedures. Hybridization was detected by antidigoxigenin rhodamine or uoresceinconjugated avidin. Correspondence and requests for materials should be addressed to F.W.A. Macmillan Magazines Ltd NATURE VOL APRIL www.nature.com Spermine treat ment of hepatocytes apparently had an inverse effect on both these cellular functions.Cultured hepa tocy tes derived from adult rats have increas ingly been used to study thebro ad spectrum of cellular reactions to chemical carcinogens. A ma jor advan tage of th is sys tem for carcinogenesisstud iesis that, under app ropri ate conditions, the se cells perform many ofthedifferentiated functions of enzymatic procarcinogen activation similarto the liver invivo. The high capacity for procarcinogen activa tion prede te rm ines the liver as an early site for the in te raction ofultima te carcinogens with cellular macromolecules and due to thecentr al role oftheliver in homeos tatic processes of the body, this organ is also a pr imary target for nu trit ional, ho rmonal, and pharmacological influences.The complex in teractions between these two processes are difficult to assess in exper imen ts wi th in tact an ima ls and requ ire simpler model sys tems. Pr imary cultures of hepa tocy tes allow for an experi men tal con trolof the se complex regu la tory influences.The costs of publication of this article were defrayed in part by the payment of page charges.This article must therefore be hereby marked advertisement in accordance with U.However,litt le is known about exogenous and endogenous influences on DNA repair in he patic and other po tential ta rgets of carcinogens.A better unders tand ing of how theremoval of DNA damage by carcin ogens th rough repair processes is regu la ted may he lp to iden tify critical even ts in tumor init iation. At the subcellu larlevel, variouslines of evidence suggest that ch romatin st ruc tu re de te rm ines the sensitivity of DNA to damage by alkylating agen ts and theaccessibility of pyrim idinedimers for UV endonuclease. However, chromatin st ruc tu re undergoes dynam ic alterations in a number of dif fe rentphysiological processes su ch asdifferentiation. A common charac ter istic of these processesis th at th ey app arently are associatedwi th changes in the nuc learactivity of. This cova lentmodification of nuc lear pro te ins could facilita te condensation and relaxation of chromatin which may be a key mechan ism involved in differentiation, DNA replication, and therecovery from DNA damage by carcinogens.