In eukaryotic cells, transcription and replication each occur on DNA templates 
that are incorporated into nucleosomes. Formation of chromatin generally limits 
accessibility of specific DNA sequences and inhibits progression of polymerases 
as they copy information from the DNA. The processes that select sites for 
initiating either transcription or replication are therefore strongly influenced 
by factors that modulate the properties of chromatin proteins. Further, in order 
to elongate their products, both DNA and RNA polymerases must be able to 
overcome the inhibition presented by chromatin (Lipford and Bell 2001; Workman 
and Kingston 1998). One way to adjust the properties of chromatin proteins is to 
covalently modify them by adding or removing chemical moieties. Both histone and 
non-histone chromatin proteins are altered by acetylation, methylation, and 
other changes, and the 'nucleosome modifying' complexes that perform these 
reactions are important components of pathways of transcriptional regulation 
(Cote 2002; Orphanides and Reinberg 2000; Roth et al. 2001; Strahl and Allis 
2000; Workman and Kingston 1998). Another way to alter the effects of 
nucleosomes is to change the position of the histone octamers relative to 
specific DNA sequences (Orphanides and Reinberg 2000; Verrijzer 2002; Wang 2002; 
Workman and Kingston 1998). Since the ability of a sequence to be bound by 
specific proteins can vary significantly whether the sequence is in the linkers 
between nucleosomes or at various positions within a nucleosome, 'nucleosome 
remodeling' complexes that rearrange nucleosome positioning are also important 
regulators of transcription. Since the DNA replication machinery has to 
encounter many of the same challenges posed by chromatin, it seems likely that 
modifying and remodeling complexes also act during duplication of the genome, 
but most of the current information on these factors relates to regulation of 
transcription. This chapter describes the factor known variously as FACT in 
humans, where it promotes elongation of RNA polymerase II on nucleosomal 
templates in vitro (Orphanides et al. 1998, 1999), DUF in frogs, where it is 
needed for DNA replication in oocyte extracts (Okuhara et al. 1999), and CP or 
SPN in yeast, where it is linked in vivo to both transcription and replication 
(Brewster et al. 2001; Formosa et al. 2001). Like the nucleosome modifying and 
remodeling complexes, it is broadly conserved among eukaryotes, affects a wide 
range of processes that utilize chromatin, and directly alters the properties of 
nucleosomes. However, it does not have nucleosome modifying or standard 
ATP-dependent remodeling activity, and therefore represents a third class of 
chromatin modulating factors. It is also presently unique in the extensive 
connections it displays with both transcription and replication: FACT/DUF/CP/SPN 
appears to modify nucleosomes in a way that is directly important for the 
efficient functioning of both RNA polymerases and DNA polymerases. While less is 
known about the mechanisms it uses to promote its functions than for other 
factors that affect chromatin, it is clearly an essential part of the complex 
mixture of activities that modulate access to DNA within chromatin. Physical and 
genetic interactions suggest that FACT/DUF/CP/SPN affects multiple pathways 
within replication and transcription as a member of several distinct complexes. 
Some of the interactions are easy to assimilate into models for replication or 
transcription, such as direct binding to DNA polymerase alpha (Wittmeyer and 
Formosa 1997; Wittmeyer et al. 1999), association with nucleosome modifying 
complexes (John et al. 2000), and interaction with factors that participate in 
elongation of RNA Polymerase II (Gavin et al. 2002; Squazzo et al. 2002). Others 
are more surprising such as an association with the 19S complex that regulates 
the function of the 20S proteasome (Ferdous et al. 2001; Xu et al. 1995), and 
the indication that FACT/DUF/CP/SPN can act as a specificity factor for casein 
kinase II (Keller et al. 2001). This chapter reviews the varied approaches that 
have each revealed different aspects of the function of FACT/DUF/CP/SPN, and 
presents a picture of a factor that can both alter nucleosomes and orchestrate 
the assembly or activity of a broad range of complexes that act upon chromatin.