Joining the PARty: PARP Regulation of KDM5A during DNA Repair (and Transcription?),BioEssays

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Joining the PARty: PARP Regulation of KDM5A during DNA Repair (and Transcription?)
BioEssays ( IF 3.2 ) Pub Date : 2022-05-09 , DOI: 10.1002/bies.202200015
Anthony Sanchez ₁ , Bethany A Buck-Koehntop ₂ , Kyle M Miller _{1,

3}

Affiliation

The lysine demethylase KDM5A collaborates with PARP1 and the histone variant macroH2A1.2 to modulate chromatin to promote DNA repair. Indeed, KDM5A engages poly(ADP-ribose) (PAR) chains at damage sites through a previously uncharacterized coiled-coil domain, a novel binding mode for PAR interactions. While KDM5A is a well-known transcriptional regulator, its function in DNA repair is only now emerging. Here we review the molecular mechanisms that regulate this PARP1-macroH2A1.2-KDM5A axis in DNA damage and consider the potential involvement of this pathway in transcription regulation and cancer. Using KDM5A as an example, we discuss how multifunctional chromatin proteins transition between several DNA-based processes, which must be coordinated to protect the integrity of the genome and epigenome. The dysregulation of chromatin and loss of genome integrity that is prevalent in human diseases including cancer may be related and could provide opportunities to target multitasking proteins with these pathways as therapeutic strategies.

中文翻译：

加入 PARty：DNA 修复（和转录？）期间 KDM5A 的 PARP 调节

赖氨酸脱甲基酶 KDM5A 与 PARP1 和组蛋白变体 MacroH2A1.2 协同调节染色质以促进 DNA 修复。事实上，KDM5A 通过先前未表征的卷曲螺旋结构域在损伤位点接合聚（ADP-核糖）（PAR）链，这是一种新的 PAR 相互作用的结合模式。虽然 KDM5A 是一种众所周知的转录调节因子，但它在 DNA 修复中的功能现在才刚刚出现。在这里，我们回顾了在 DNA 损伤中调节 PARP1-macroH2A1.2-KDM5A 轴的分子机制，并考虑了该通路在转录调节和癌症中的潜在参与。以 KDM5A 为例，我们讨论多功能染色质蛋白如何在多个基于 DNA 的过程之间转换，这些过程必须协调以保护基因组和表观基因组的完整性。

更新日期：2022-05-09

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