Our manuscript describing a 10bp mutation rate periodicity within nucleosome-covered DNA is out in @CellCellPress. [1/11]
authors.elsevier.com/a/1X~jBL7PXUj6c
authors.elsevier.com/a/1X~jBL7PXUj6c
We found that tumor somatic mutation rate has a strong 10bp periodicity, which follows the orientation of the DNA minor groove towards or away from histones. [2/11]
We were surprised when we realised that different cancer types have signals with opposite phase. For instance, esophageal tumors have more mutations at minor groove facing histones, while melanomas at minor groove away from histones [3/11]
We then studied the periodicity of mutations contributed by different mutational signatures to understand how DNA wrapping around nucleosomes influences different mutational processes [4/11]
We revealed a complex interplay between DNA damage and repair in nucleosome-covered DNA: Periodic UV-light induced damage (more CPDs and 6-4PPs in minor-out) and periodic Nucleotide Excision Repair and Base Excision Repair (more efficient repair in minor-out) [5/11]
We then analized germline variation and interspecific divergence in primates and plants and found a clear periodicity, higher variation and divergence at minor groove facing histones [6/11]
We realised this 10bp mutation rate periodicity could explain the 10bp periodicity in A/T di-nucleotides in eukaryotic genomes (higher rate of A/T pairs every 10bp, at minor groove facing histones, traditionally attributed to favorable bending of DNA around histones) [7/11]
In summary, we propose that the 10bp mutation rate periodicity, together with the bias towards C>T germline mutations, has contributed to create the WW periodicity in eukaryotic genomes [8/11]
Read also the nice News & Views of our paper by @segal_eran and Eran Kotler. [9/11] cell.com/cell/fulltext/…
We aim for fully reproducible science. Data and code to reproduce all analyses and generate figures of the paper are open at bitbucket.org/bbglab/nucleos…. [10/11]
This has been an extremely fun and exciting project to work on with an amazing team of scientist. @oriol_pich @fmuinos @r_sabarinathan Iker Reyes and Abel Gonzalez-Perez [11/11]
