Although the overall picture of humancytomegalovirus (HHV-5) DNA synthesis appears typical of the herpesviruses, some novel features are emerging.
Structure
In ICP8, the
herpes simplex virus (HSV-1)
single-strand DNA-binding protein (ssDNA-binding protein (SSB)), the head consists of the eight
alpha helices. The front side of the neck region consists of a five-stranded
beta-sheet and two alpha helices, whereas the back side is a three-stranded beta-sheet The shoulder part of the
N-terminal domain contains an alpha-helical and beta-sheet region.[1] The
herpes simplex virus (HSV-1) SSB, ICP8, is a nuclear protein that, along other replication proteins is required for viral DNA replication during lytic infection.[1]
Mechanism
Six herpes virus-group-common
genes encode
proteins that likely constitute the
replication fork machinery, including a two-subunit DNA polymerase, a
Helicase-primase complex and a single-stranded DNA-binding protein.[2] The humanherpesvirus 1 (HHV-1) single-strand DNA-binding protein ICP8 is a 128kDa
zincmetalloprotein.
Photoaffinity labeling has shown that the region encompassing
amino acid residues 368-902 contains the single-strand DNA-binding site of ICP8.[3] The HHHV-1 UL5, UL8, and UL52
genes encode an essential
heterotrimeric DNA helicase-primase that is responsible for concomitant DNA unwinding and
primer synthesis at the
viral DNA replication fork. ICP8 may stimulate DNA unwinding and enable bypass of cisplatin damaged DNA by recruiting the helicase-primase to the DNA.[4]
Replication protein A is the functional equivalent of SSB in the nucleus of eukaryotic cells, though there is no sequence homology.
Eukaryotic mitochondrial SSB
The mitochondria of eukaryotic cells contain their own single stranded DNA binding protein. Human mitochondrial SSB (mtSSB) binds to single-stranded mitochondrial DNA as a tetramer and has sequence similarity to bacterial SSB.[7] Human mtSSB is encoded by the
SSBP1 gene. In yeast, it is encoded by the RIM1 gene.[8]
Role in Genome Repair and Anti-aging
Recently, it has been found that it 1. Helps protect the genome, 2. Is vital for stem cells and 3. Is involved with maintaining telomere length.[9][10][11]
^Anders DG, McCue LA (1996). "The human cytomegalovirus genes and proteins required for DNA synthesis". Intervirology. 39 (5–6): 378–88.
doi:
10.1159/000150508.
PMID9130047.
^Tiranti, V; Rocchi, M; DiDonato, S; Zeviani, M (30 April 1993). "Cloning of human and rat cDNAs encoding the mitochondrial single-stranded DNA-binding protein (SSB)". Gene. 126 (2): 219–25.
doi:
10.1016/0378-1119(93)90370-i.
PMID8482537.