Transcription-Coupled Nucleotide Excision Repair and the Transcriptional Response to UV-Induced DNA Damage
Annu Rev Biochem. 2023 Apr 11. doi: 10.1146/annurev-biochem-052621-091205. Online ahead of print.ABSTRACTUltraviolet (UV) irradiation and other genotoxic stresses induce bulky DNA lesions, which threaten genome stability and cell viability. Cells have evolved two main repair pathways to remove such lesions: global genome nucleotide excision repair (GG-NER) and transcription-coupled nucleotide excision repair (TC-NER). The modes by which these subpathways recognize DNA lesions are distinct, but they converge onto the same downstream steps for DNA repair. Here, we first summarize the current understanding of these repair mec...
Source: Annual Review of Biochemistry - April 11, 2023 Category: Biochemistry Authors: Nicol ás Nieto Moreno Anouk M Olthof Jesper Q Svejstrup Source Type: research

The Design and Application of DNA-Editing Enzymes as Base Editors
Annu Rev Biochem. 2023 Apr 5. doi: 10.1146/annurev-biochem-052521-013938. Online ahead of print.ABSTRACTDNA-editing enzymes perform chemical reactions on DNA nucleobases. These reactions can change the genetic identity of the modified base or modulate gene expression. Interest in DNA-editing enzymes has burgeoned in recent years due to the advent of clustered regularly interspaced short palindromic repeat-associated (CRISPR-Cas) systems, which can be used to direct their DNA-editing activity to specific genomic loci of interest. In this review, we showcase DNA-editing enzymes that have been repurposed or redesigned and dev...
Source: Annual Review of Biochemistry - April 5, 2023 Category: Biochemistry Authors: Kartik L Rallapalli Alexis C Komor Source Type: research

mRNA Regulation by RNA Modifications
Annu Rev Biochem. 2023 Apr 5. doi: 10.1146/annurev-biochem-052521-035949. Online ahead of print.ABSTRACTChemical modifications on mRNA represent a critical layer of gene expression regulation. Research in this area has continued to accelerate over the last decade, as more modifications are being characterized with increasing depth and breadth. mRNA modifications have been demonstrated to influence nearly every step from the early phases of transcript synthesis in the nucleus through to their decay in the cytoplasm, but in many cases, the molecular mechanisms involved in these processes remain mysterious. Here, we highlight...
Source: Annual Review of Biochemistry - April 5, 2023 Category: Biochemistry Authors: Wendy V Gilbert Sigrid Nachtergaele Source Type: research

Polyamines in Parkinson's Disease: Balancing Between Neurotoxicity and Neuroprotection
Annu Rev Biochem. 2023 Apr 5. doi: 10.1146/annurev-biochem-071322-021330. Online ahead of print.ABSTRACTThe polyamines putrescine, spermidine, and spermine are abundant polycations of vital importance in mammalian cells. Their cellular levels are tightly regulated by degradation and synthesis, as well as by uptake and export. Here, we discuss the delicate balance between the neuroprotective and neurotoxic effects of polyamines in the context of Parkinson's disease (PD). Polyamine levels decline with aging and are altered in patients with PD, whereas recent mechanistic studies on ATP13A2 (PARK9) demonstrated a driving role ...
Source: Annual Review of Biochemistry - April 5, 2023 Category: Biochemistry Authors: Stephanie Vrijsen Marine Houdou Ana Cascalho Jan Eggermont Peter Vangheluwe Source Type: research

Mechanism of Radical Initiation in the Radical SAM Enzyme Superfamily
Annu Rev Biochem. 2023 Apr 5. doi: 10.1146/annurev-biochem-052621-090638. Online ahead of print.ABSTRACTRadical S-adenosylmethionine (SAM) enzymes use a site-differentiated [4Fe-4S] cluster and SAM to initiate radical reactions through liberation of the 5'-deoxyadenosyl (5'-dAdo•) radical. They form the largest enzyme superfamily, with more than 700,000 unique sequences currently, and their numbers continue to grow as a result of ongoing bioinformatics efforts. The range of extremely diverse, highly regio- and stereo-specific reactions known to be catalyzed by radical SAM superfamily members is remarkable. The common mec...
Source: Annual Review of Biochemistry - April 5, 2023 Category: Biochemistry Authors: Brian M Hoffman William E Broderick Joan B Broderick Source Type: research