UV is a significant environmental agent that damages DNA. Translesion synthesis (TLS) is a DNA damage tolerance pathway that utilizes specialized DNA polymerases to replicate through the damaged DNA, often leading to mutagenesis. In eukaryotic cells, genomic DNA is organized into chromatin that is composed of nucleosomes. To date, if and/or how TLS is regulated by a specific nucleosome feature has been undocumented. We found that mutations of multiple histone H4 residues mostly or entirely embedded in the nucleosomal LRS (loss of ribosomal DNA-silencing) domain attenuate UV mutagenesis in Saccharomyces cerevisiae. The attenuation is not caused by an alteration of ubiquitination or sumoylation of PCNA (proliferating cell nuclear antigen), the modifications well-known to regulate TLS. Also, the attenuation is not caused by decreased chromatin accessibility, or by alterations of methylation of histone H3 K79, which is at the center of the LRS surface. The attenuation may result from compromised TLS by both DNA polymerases ζ and η, in which Rad6 and Rad5 are but Rad18 is not implicated. We propose that a feature of the LRS is recognized or accessed by the TLS machineries either during/after a nucleosome is disassembled in front of a lesion-stalled replication fork, or during/before a nucleosome is reassembled behind a lesion-stalled replication fork.

紫外线是破坏DNA的重要环保剂。跨病变合成（TLS）是一种DNA损伤耐受途径，该途径利用专门的DNA聚合酶在受损的DNA中复制，通常导致诱变。在真核细胞中，基因组DNA被组织成由核小体组成的染色质。迄今为止，尚未证明是否和/或如何通过特定的核小体特征调节TLS。我们发现多个组蛋白H4残基的突变大部分或完全嵌入核小体LRS（核糖体DNA沉默）域中，从而减弱了酿酒酵母中的紫外线诱变。。衰减不是由PCNA（增殖细胞核抗原）的泛素化或磺酰化改变引起的，PCNA是众所周知的调节TLS的修饰。同样，衰减不是由于染色质可及性降低，也不是由于LRS表面中心的组蛋白H3 K79的甲基化改变所致。衰减可能是由于DNA聚合酶ζ和η都破坏了TLS而引起的，其中Rad6和Rad5参与其中，但Rad18不参与其中。我们建议TLS机器识别或访问LRS的功能是在核小体在病变固定的复制叉之前被拆卸的过程中/之后，或在核小体被病变固定的复制叉后面重新装配的过程中/之前。