HAATI survivors replace canonical telomeres with blocks of generic heterochromatin.

The notion that telomeres are essential for chromosome linearity stems from the existence of two chief dangers: inappropriate DNA damage response (DDR) reactions that mistake natural chromosome ends for double-strand DNA breaks (DSBs), and the progressive loss of DNA from chromosomal termini due to the end replication problem. Telomeres avert the former peril by binding sequence-specific end-protection factors that control the access of DDR activities. The latter threat is tackled by recruiting telomerase, a reverse transcriptase that uses an integral RNA subunit to template the addition of telomere repeats to chromosome ends. Here we describe an alternative mode of linear chromosome maintenance in which canonical telomeres are superseded by blocks of heterochromatin. We show that in the absence of telomerase, Schizosaccharomyces pombe cells can survive telomere sequence loss by continually amplifying and rearranging heterochromatic sequences. Because the heterochromatin assembly machinery is required for this survival mode, we have termed it 'HAATI' (heterochromatin amplification-mediated and telomerase-independent). HAATI uses the canonical end-protection protein Pot1 (ref. 4) and its interacting partner Ccq1 (ref. 5) to preserve chromosome linearity. The data suggest a model in which Ccq1 is recruited by the amplified heterochromatin and provides an anchor for Pot1, which accomplishes its end-protection function in the absence of its cognate DNA-binding sequence. HAATI resembles the chromosome end-maintenance strategy found in Drosophila melanogaster, which lacks specific telomere sequences but nonetheless assembles terminal heterochromatin structures that recruit end-protection factors. These findings reveal a previously unrecognized mode by which cancer cells might escape the requirement for telomerase activation, and offer a tool for studying genomes that sustain unusually high levels of heterochromatinization.

Coxsackievirus B3 sequences in the blood of a neonate with congenital myocarditis, plus serological evidence of maternal infection.

A fatal case of myocarditis in a neonate is described. The clinical features were evident at birth, and enteroviral RNA was detected in the blood of the baby on the day of birth and again 10 days later by a generic enterovirus nested reverse transcription-polymerase chain reaction (RT-PCR) assay. The enterovirus RNA was subsequently retested by a separate, newly developed nested RT-PCR assay yielding a PCR product within the VP1 coding region suitable for sequencing. Identical 239-base pair sequences were obtained from the RNA of the two blood samples and this sequence most closely resembled coxsackievirus B3 (94% identity). The baby's mother was pyrexial immediately postpartum and an early antenatal serum and a serum sample collected 10 days postpartum tested in parallel for enterovirus IgM antibody showed negative to strong-positive seroconversion. Infection of the mother was the likely primary event with in utero transfer of the virus to the fetus in the last few days of pregnancy. Neonatal blood is a valuable specimen for enterovirus diagnosis by RT-PCR. A newly developed nested RT-PCR assay was successful in typing the enterovirus from stored RNA extracted directly from the blood samples. Serology for enterovirus IgM antibody can be useful for convalescent diagnosis of enterovirus infection in the mother, especially with earlier serum for comparison.