PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity.
Proliferating cell nuclear antigen (PCNA) is a maestro of DNA replication. PCNA forms a homotrimer and interacts with various proteins, such as DNA polymerases, DNA ligase I (LIG1), and flap endonuclease 1 (FEN1) for faithful DNA replication. Here, we identify the crucial role of Ser46-Leu47 residue...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0285337 |
| _version_ | 1797805726397104128 |
|---|---|
| author | Sangin Kim Yeongjae Kim Youyoung Kim Suhyeon Yoon Kyoo-Young Lee Yoonsung Lee Sukhyun Kang Kyungjae Myung Chang-Kyu Oh |
| author_facet | Sangin Kim Yeongjae Kim Youyoung Kim Suhyeon Yoon Kyoo-Young Lee Yoonsung Lee Sukhyun Kang Kyungjae Myung Chang-Kyu Oh |
| author_sort | Sangin Kim |
| collection | DOAJ |
| description | Proliferating cell nuclear antigen (PCNA) is a maestro of DNA replication. PCNA forms a homotrimer and interacts with various proteins, such as DNA polymerases, DNA ligase I (LIG1), and flap endonuclease 1 (FEN1) for faithful DNA replication. Here, we identify the crucial role of Ser46-Leu47 residues of PCNA in maintaining genomic integrity using in vitro, and cell-based assays and structural prediction. The predicted PCNAΔSL47 structure shows the potential distortion of the central loop and reduced hydrophobicity. PCNAΔSL47 shows a defective interaction with PCNAWT leading to defects in homo-trimerization in vitro. PCNAΔSL47 is defective in the FEN1 and LIG1 interaction. PCNA ubiquitination and DNA-RNA hybrid processing are defective in PCNAΔSL47-expressing cells. Accordingly, PCNAΔSL47-expressing cells exhibit an increased number of single-stranded DNA gaps and higher levels of γH2AX, and sensitivity to DNA-damaging agents, highlighting the importance of PCNA Ser46-Leu47 residues in maintaining genomic integrity. |
| first_indexed | 2024-03-13T05:56:25Z |
| format | Article |
| id | doaj.art-e652c86ea5074c2caa1aada76b207e76 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-13T05:56:25Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-e652c86ea5074c2caa1aada76b207e762023-06-13T05:31:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01185e028533710.1371/journal.pone.0285337PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity.Sangin KimYeongjae KimYouyoung KimSuhyeon YoonKyoo-Young LeeYoonsung LeeSukhyun KangKyungjae MyungChang-Kyu OhProliferating cell nuclear antigen (PCNA) is a maestro of DNA replication. PCNA forms a homotrimer and interacts with various proteins, such as DNA polymerases, DNA ligase I (LIG1), and flap endonuclease 1 (FEN1) for faithful DNA replication. Here, we identify the crucial role of Ser46-Leu47 residues of PCNA in maintaining genomic integrity using in vitro, and cell-based assays and structural prediction. The predicted PCNAΔSL47 structure shows the potential distortion of the central loop and reduced hydrophobicity. PCNAΔSL47 shows a defective interaction with PCNAWT leading to defects in homo-trimerization in vitro. PCNAΔSL47 is defective in the FEN1 and LIG1 interaction. PCNA ubiquitination and DNA-RNA hybrid processing are defective in PCNAΔSL47-expressing cells. Accordingly, PCNAΔSL47-expressing cells exhibit an increased number of single-stranded DNA gaps and higher levels of γH2AX, and sensitivity to DNA-damaging agents, highlighting the importance of PCNA Ser46-Leu47 residues in maintaining genomic integrity.https://doi.org/10.1371/journal.pone.0285337 |
| spellingShingle | Sangin Kim Yeongjae Kim Youyoung Kim Suhyeon Yoon Kyoo-Young Lee Yoonsung Lee Sukhyun Kang Kyungjae Myung Chang-Kyu Oh PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity. PLoS ONE |
| title | PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity. |
| title_full | PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity. |
| title_fullStr | PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity. |
| title_full_unstemmed | PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity. |
| title_short | PCNA Ser46-Leu47 residues are crucial in preserving genomic integrity. |
| title_sort | pcna ser46 leu47 residues are crucial in preserving genomic integrity |
| url | https://doi.org/10.1371/journal.pone.0285337 |
| work_keys_str_mv | AT sanginkim pcnaser46leu47residuesarecrucialinpreservinggenomicintegrity AT yeongjaekim pcnaser46leu47residuesarecrucialinpreservinggenomicintegrity AT youyoungkim pcnaser46leu47residuesarecrucialinpreservinggenomicintegrity AT suhyeonyoon pcnaser46leu47residuesarecrucialinpreservinggenomicintegrity AT kyooyounglee pcnaser46leu47residuesarecrucialinpreservinggenomicintegrity AT yoonsunglee pcnaser46leu47residuesarecrucialinpreservinggenomicintegrity AT sukhyunkang pcnaser46leu47residuesarecrucialinpreservinggenomicintegrity AT kyungjaemyung pcnaser46leu47residuesarecrucialinpreservinggenomicintegrity AT changkyuoh pcnaser46leu47residuesarecrucialinpreservinggenomicintegrity |