Effects of replication domains on genome-wide UV-induced DNA damage and repair.
Effects of replication domains on genome-wide UV-induced DNA damage and repair.
复制标题
复制域对全基因组紫外线诱导的 DNA 损伤和修复的影响
DOI：
10.1371/journal.pgen.1010426
复制
发表时间：
2022-09
期刊：
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
--
作者：
核苷酸切除修复是去除胎盘中UV诱导的DNA损伤的主要修复机制。未修复的紫外线诱导的损伤可能导致DNA复制过程中的突变。虽然嘧啶二聚体的诱变是合理的理解，复制叉进展对核苷酸切除修复的直接影响还有待澄清。在这里，我们应用了Damage-seq和XR-seq技术，并在同步UV处理的HeLa细胞中生成了复制图谱。结果表明，正在进行的复制在早期和晚期复制域刺激局部修复。此外，据透露，滞后链模板上的损伤在后期复制结构域中修复较慢，这可能是由于不平衡的序列背景。不对称的相对修复与黑色素瘤突变的链偏好一致，表明外源性损伤、修复和复制在突变链不对称中的作用。UV诱导的损伤可在DNA复制期间引起突变，并且复制和修复之间的串扰可影响诱变。通过整合全基因组损伤、修复和复制图谱，我们研究了复制结构域对核苷酸切除修复的影响。由于开放的染色质，早期复制结构域修复得更快;因此，它们具有更少的突变。此外，修复水平显示链的不对称性在后期复制域的起始区，有利于独立于正在进行的复制的主导链。然而，后期复制域的起始区具有高AT含量，并表现出较强的链不对称性，在滞后链上具有更多的T-束。因此，这种与黑色素瘤突变不对称性相一致的偏向性修复可能是由导致更高CPD形成和减少修复的序列含量引起的。我们的研究结果表明，不对称损伤的形成和修复有助于复制起始区周围的诱变不对称性。
Nucleotide excision repair is the primary repair mechanism that removes UV-induced DNA lesions in placentals. Unrepaired UV-induced lesions could result in mutations during DNA replication. Although the mutagenesis of pyrimidine dimers is reasonably well understood, the direct effects of replication fork progression on nucleotide excision repair are yet to be clarified. Here, we applied Damage-seq and XR-seq techniques and generated replication maps in synchronized UV-treated HeLa cells. The results suggest that ongoing replication stimulates local repair in both early and late replication domains. Additionally, it was revealed that lesions on lagging strand templates are repaired slower in late replication domains, which is probably due to the imbalanced sequence context. Asymmetric relative repair is in line with the strand bias of melanoma mutations, suggesting a role of exogenous damage, repair, and replication in mutational strand asymmetry. UV-induced damage can cause mutations during DNA replication, and crosstalk between replication and repair may influence mutagenesis. By integrating genome-wide damage, repair, and replication maps, we investigated the effects of replication domains on nucleotide excision repair. Early replication domains are repaired faster due to open chromatin; thus, they harbor fewer mutations. In addition, repair levels show strand asymmetry in the initiation zones of late replication domains, favoring leading strands independent of the ongoing replication. However, initiation zones of late replication domains have high AT content and exhibit a strong strand asymmetry with more T-tracts on lagging strands. Therefore, this biased repair, which coincides with melanoma mutational asymmetry, could be caused by a sequence content that leads to higher CPD formation and reduced repair. Our findings suggest that asymmetric damage formation and repair contribute to mutagenesis asymmetry around replication initiation zones.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
64.5
作者：
Haradhvala NJ;Polak P;Stojanov P;Covington KR;Shinbrot E;Hess JM;Rheinbay E;Kim J;Maruvka YE;Braunstein LZ;Kamburov A;Hanawalt PC;Wheeler DA;Koren A;Lawrence MS;Getz G
通讯作者：
Getz G
DOI：
10.1073/pnas.1614430113
发表时间：
2016-10-11
影响因子：
11.1
作者：
Hu, Jinchuan;Lieb, Jason D.;Adar, Sheera
通讯作者：
Adar, Sheera
DOI：
10.1073/pnas.1706522114
发表时间：
2017-06-27
影响因子：
11.1
作者：
Hu, Jinchuan;Adebali, Ogun;Sancar, Aziz
通讯作者：
Sancar, Aziz
影响因子：
5.6
作者：
Duc C;Thiriet C
通讯作者：
Thiriet C