{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe provided collection of abstracts does not mention RIMS4. Instead, they focus on specialized translesion synthesis (TLS) DNA polymerases—including REV1, Polkappa, Poliota, and others—and their roles in bypassing DNA lesions to preserve genome integrity. In these studies, REV1 is shown to act as an essential scaffolding protein that coordinates multiple TLS polymerases via its C‐terminal domain, which interacts with short “REV1‐interacting regions” (RIRs) present in Polkappa, Poliota, and other Y‐family polymerases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " This network of interactions facilitates nucleotide insertion opposite various DNA lesions such as UV–induced photoproducts, bulky chemical adducts, and oxidative modifications, thereby allowing replication to proceed despite template damage.\n \nFurther structural and functional analyses reveal that REV1’s C-terminal domain adopts a defined fold upon binding RIR peptides and simultaneously provides a binding surface for the Rev7 subunit of DNA polymerase ζ, a key participant in extending from the inserted nucleotide."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": " Meanwhile, Polkappa not only contributes to the direct bypass of specific lesions—such as bulky benzo[a]pyrene adducts and oxidatively damaged bases—but also appears to have roles in additional repair pathways including nucleotide excision repair and replication fork recovery. Its activity is modulated by interactions with monoubiquitinated PCNA and may require its unique structural domains (e.g., the N-clasp) for efficient and accurate TLS."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n \nIn vivo studies spanning various mouse genetic models further underscore the physiological significance of these polymerases. For example, loss-of-function or inactivation of Polkappa results in enhanced sensitivity to a range of DNA-damaging agents, increased mutation frequencies, and aberrant checkpoint activation, which together signify its crucial role in accurate lesion bypass and genome maintenance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": " Complementary studies have dissected the structural determinants enabling these polymerases to interact, revealing that minor alterations in their interaction motifs or catalytic domains can markedly affect their biochemical activity and the overall TLS process."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "14"}]}, {"type": "t", "text": "\n \nFurther structural characterization of the REV1 C-terminal domain and its complex with the RIR of Polkappa has provided detailed insights into how this assembly orchestrates the switch between the insertion and extension steps during TLS, a mechanism that is critical for minimizing mutagenesis while allowing replication to continue past DNA damage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "17"}]}, {"type": "t", "text": " Additional work comparing variant forms of Polkappa emphasizes that specific regions—including its extreme N-terminal sequences—are required not only for maintaining catalytic efficiency and fidelity during TLS but also for proper recovery from replication stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "20"}]}, {"type": "t", "text": "\n \nFinally, investigations into the genotoxic response in Polkappa-mutant mice highlight that while Polkappa is critical for suppressing mutations induced by various environmental carcinogens, its absence can lead to distinct mutation signatures in different tissues, thus confirming its multifaceted role in DNA damage tolerance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "\n \nIn summary, although none of these studies provide information on RIMS4, they collectively demonstrate that the coordinated function and regulation of specialized TLS polymerases—through precise protein–protein interactions and domain-specific structural features—are essential for efficient lesion bypass, genome stability, and cell survival in the face of DNA damage.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tomoo Ogi, Yoichi Shinkai, Kiyoji Tanaka, et al. 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