AIDS Research: HIV-1 Acquired a Cellular Gene to Promote Viral Replication. Examining a critical step in viral replication called minus strand transfer, we found that it involves circularization of the viral RNA. Using high speed computing and computational biology methods, we discovered that the sequences involved in the circularization included a small gene, apparently acquired by the virus thousands of years ago from the genome of an infected host. The gene has been retained in recognizable forms, because it is a rare example of a host gene that has been hijacked by a virus to support viral replication. The gene sequence suggests that HIV evolved first in African cats, before being transferred to monkeys and humans. Moreover, the presence of the gene in only some monkey viruses, suggests that it could make the difference between viruses causing virulent rather than latent infections. Future work involves molecular paleontology of the gene and examination of its role in promoting virus growth.
Carcinogenesis: Mechanisms of DNA Repair and Replication. Human cells defend against aging and cancer by accurate replication of DNA and efficient DNA repair. We recently discovered that human cells have developed a unique mechanism to protect the information in genes that express proteins in active chromatin. The same acetyl-transferase that makes regions of chromatin more accessible for transcription alters the functions of specific replication and repair proteins. These proteins become extra-efficient at removing lesions in the DNA, and preventing replication errors, but only in active genes. These results indicate that the cells can regulate the effectiveness with which they protect DNA from aging. This finding offers a unique opportunity to influence that regulation to delay the onset of cancers by up-regulating the efficiency with which we protect our DNA. Future work will involve investigating the mechanisms of the regulation in cells, biochemical assays, and in reconstituted chromatin.