Involvement of p29 in DNA damage responses and Fanconi anemia pathway

Po-Chen Chu1, Tao-Yeuan Wang, Yen-Ta Lu

  • 1Institute of Biochemical Sciences, National Taiwan University, No. 1, Section 4, Taipei, Taiwan.

Carcinogenesis
|September 15, 2009
PubMed

Insights

Human p29 protein plays a role in DNA damage response and the Fanconi anemia pathway. Silencing p29 affects cell cycle progression, while its expression aids in DNA repair mechanisms and reduces tumor incidence post-UV exposure.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • p29 is a chromatin-associated protein.
  • p29's role in DNA damage response and Fanconi anemia pathway requires further elucidation.

Purpose of the Study:

  • To characterize the function of human p29 in DNA damage response.
  • To investigate p29's involvement in the Fanconi anemia pathway.

Main Methods:

  • Established U2OS and Fanconi anemia complementation group G (FA-G) cells with constitutive p29 expression.
  • Analyzed Chk1/Chk2 phosphorylation, Mre11-Rad50-Nbs1 complex, ATR-IP, and FA ID complex monoubiquitination.
  • Assessed tumor incidence in mp29 transgenic mice after UV irradiation.

Main Results:

  • p29 silencing increased G1 phase cell population and decreased Chk1/Chk2 phosphorylation.
  • Constitutive p29 expression elevated Chk1/Chk2 phosphorylation, Mre11-Rad50-Nbs1, and ATR-IP.
  • p29 expression restored FA ID complex monoubiquitination in FA-G cells and reduced tumor incidence in mice post-UV.

Conclusions:

  • p29 is involved in DNA damage responses.
  • p29 plays a role in the Fanconi anemia pathway.
  • p29 may function as a tumor suppressor in response to UV-induced DNA damage.

Related Concept Videos

DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.