Maurya, P. K. | Search bioRxiv

bioRxiv2021

SARS-CoV-2 genome sequences from Lucknow, Uttar Pradesh, India by Nanopore Sequencing

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as a significant challenge worldwide. Rapid genome sequencing of SARS-CoV-2 is going on across the globe to detect mutations and genomic modifications in SARS-CoV-2. In this study, we have sequenced twenty-three SARS-CoV-2 positive samples collected during the first pandemic from the state of Uttar Pradesh, India. We observed a range of already reported mutations (2-22), including; D614G, L452R, Q613H, Q677H, T1027I in the S gene; S194L in the N gene; Q57H, L106F, T175I in the ORF3. Few unreported mutations such as P309S in the ORF1ab gene; T379I in the N gene; and L52F, V77I in the ORF3a gene were also detected. Phylogenetic genome analysis showed similarity with other SARS-CoV-2 viruses reported from Uttar Pradesh. The observed mutations may be associated with SARS-CoV-2 virus pathogenicity or disease severity.

genomics↗

bioRxiv2021

RTT109 AND Fun30 proteins mediate epigenetic regulation of the DNA damage response pathway in C. albicans

Fun30, an ATP-dependent chromatin remodeller, from S. cerevisiae mediates both regulation of gene expression as well as DNA damage response/repair. In this paper, we have characterized the biochemical and physiological function of Fun30 from the opportunistic fungi, C. albicans. Biochemically, the protein shows DNA-stimulated ATPase activity. Physiologically, the protein co-regulates transcription of RTT109, TEL1, MEC1, and SNF2-genes that encode for proteins involved in DNA damage response and repair pathway. The expression of FUN30, in turn, is regulated by histone H3 acetylation catalysed by Rtt109 encoded by RTT109. The RTT109Hz/FUN30Hz mutant strain shows sensitivity to oxidative stress and resistance to MMS as compared to the wild type strain. Quantitative PCR showed that the sensitivity to oxidative stress results from downregulation of MEC1, RAD9, MRC1 and RAD5 expression; ChIP experiments showed Fun30 but not H3ac regulates the expression of these genes in response to oxidative stress. In contrast, on treatment with MMS, the expression of RAD9 is upregulated and this upregulation is co-regulated by both Fun30 and H3 acetylation catalysed by Rtt109. Thus, Fun30 and H3 acetylation mediate the response of the fungal cell to genotoxic agents in C. albicans by regulating the expression of DNA damage response and repair pathway genes.

molecular biology↗